receptor protein interaction: Topics by Science.gov tiffany hjärta

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  1. Muscarinic receptor family interacting proteins: role in receptor function.

    PubMed

    Borroto-Escuela, Dasiel O; Correia, Patrícia A; Romero-Fernandez, Wilber; Narvaez, Manuel; Fuxe, Kjell; Ciruela, Francisco; Garriga, Pere

    2011-02-15

    G protein-coupled receptors constitute one of the most important families of membrane receptors through which cells respond to extracellular stimuli. Receptors of this superfamily likely function as signal transduction complexes. The identification and analysis of their components provide new insights into a better understanding of these receptors' function and regulation. We used tandem-affinity purification and mass spectrometry as a systematic approach to characterize multiprotein complexes in the acetylcholine muscarinic receptor subfamily. To overcome the limitations associated with membrane protein receptor solubilization with detergents, we developed a strategy in which receptors are co-expressed with a cytoplasmic minigene construct, encoding the third intracellular loop and the C-terminal tail tagged to the tandem-affinity-cassette of each receptor subtype. Numerous protein complexes were identified, including many new interactions in various signalling pathways. Systematic identification data set together with protein interactions reported in the literature revealed a high degree of connectivity. These allow the proposal, for the first time, of an outline of the muscarinic interactome as a network of protein complexes and a context for a more reasoned and informed approach to drug discovery and muscarinic receptor subtype specificities.

  2. Metabotropic Glutamate Receptors and Interacting Proteins in Epileptogenesis

    PubMed Central

    Qian, Feng; Tang, Feng-Ru

    2016-01-01

    Neurotransmitter and receptor systems are involved in different neurological and neuropsychological disorders such as Parkinson's disease, depression, Alzheimer’s disease and epilepsy. Recent advances in studies of signal transduction pathways or interacting proteins of neurotransmitter receptor systems suggest that different receptor systems may share the common signal transduction pathways or interacting proteins which may be better therapeutic targets for development of drugs to effectively control brain diseases. In this paper, we reviewed metabotropic glutamate receptors (mGluRs) and their related signal transduction pathways or interacting proteins in status epilepticus and temporal lobe epilepsy, and proposed some novel therapeutical drug targets for controlling epilepsy and epileptogenesis. PMID:27030135

  3. The Two Faces of Receptor Interacting Protein Kinase-1

    PubMed Central

    Weinlich, Ricardo; Green, Douglas R.

    2014-01-01

    Receptor Interacting Protein Kinase-1 (RIPK1), a key player in inflammation and cell death, assumes opposite functions depending on the cellular context and its posttranslational modifications. Genetic evidence supported by biochemical and cellular biology approaches shed light on the circumstances in which RIPK1 promotes or inhibits these processes. PMID:25459879

  4. Group I Metabotropic Glutamate Receptor Interacting Proteins: Fine-Tuning Receptor Functions in Health and Disease

    PubMed Central

    Kalinowska, Magdalena; Francesconi, Anna

    2016-01-01

    Group I metabotropic glutamate receptors mediate slow excitatory neurotransmission in the central nervous system and are critical to activity-dependent synaptic plasticity, a cellular substrate of learning and memory. Dysregulated receptor signaling is implicated in neuropsychiatric conditions ranging from neurodevelopmental to neurodegenerative disorders. Importantly, group I metabotropic glutamate receptor signaling functions can be modulated by interacting proteins that mediate receptor trafficking, expression and coupling efficiency to signaling effectors. These interactions afford cell- or pathway-specific modulation to fine-tune receptor function, thus representing a potential target for pharmacological interventions in pathological conditions. PMID:27296642

  5. Interaction of G protein coupled receptors and cholesterol.

    PubMed

    Gimpl, Gerald

    2016-09-01

    G protein coupled receptors (GPCRs) form the largest receptor superfamily in eukaryotic cells. Owing to their seven transmembrane helices, large parts of these proteins are embedded in the cholesterol-rich plasma membrane bilayer. Thus, GPCRs are always in proximity to cholesterol. Some of them are functionally dependent on the specific presence of cholesterol. Over the last years, enormous progress on receptor structures has been achieved. While lipophilic ligands other than cholesterol have been shown to bind either inside the helix bundle or at the receptor-lipid interface, the binding site of cholesterol was either a single transmembrane helix or a groove between two or more transmembrane helices. A clear preference for one of the two membrane leaflets has not been observed. Not surprisingly, many hydrophobic residues (primarily leucine and isoleucine) were found to be involved in cholesterol binding. In most cases, the rough β-face of cholesterol contacted the transmembrane helix bundle rather than the surrounding lipid matrix. The polar hydroxy group of cholesterol was localized near the water-membrane interface with potential hydrogen bonding to residues in receptor loop regions. Although a canonical motif, designated as CCM site, was detected as a specific cholesterol binding site in case of the β2AR, this site was not found to be occupied by cholesterol in other GPCRs possessing the same motif. Cholesterol-receptor interactions can increase the compactness of the receptor structure and are able to enhance the conformational stability towards active or inactive receptor states. Overall, all current data suggest a high plasticity of cholesterol interaction sites in GPCRs.

  6. Treponema pallidum receptor binding proteins interact with fibronectin

    PubMed Central

    1983-01-01

    Analysis of plasma proteins avidly bound to T. pallidum surfaces revealed the ability of T. pallidum to acquire numerous host macromolecules. No acquisition was evident by the avirulent spirochete, T. phagedenis biotype Reiter. Western blotting technology using hyperimmune antifibronectin serum as a probe revealed the ability of virulent treponemes to avidly bind fibronectin from a complex medium such as plasma. The specificity of the tiplike adherence of motile T. pallidum to fibronectin-coated glass surfaces and to fibronectin on HEp- 2 cells was reinforced by the observation that pretreatment of coverslips or cell monolayers with monospecific antiserum against fibronectin substantially reduced T. pallidum attachment. The stoichiometric binding of T. pallidum to fibronectin-coated coverslips and the inability of unlabeled or 35S-radiolabeled treponemes to interact with glass surfaces treated with other plasma proteins further established the specific nature of the interaction between virulent T. pallidum and fibronectin. The avid association between three outer envelope proteins of T. pallidum and fibronectin was also demonstrated. These treponemal surface proteins have been previously identified as putative receptor-binding proteins responsible for T. pallidum parasitism of host cells. The data suggest that surface fibronectin mediates tip-oriented attachment of T. pallidum to host cells via a receptor-ligand mechanism of recognition. PMID:6304227

  7. Huntingtin-Interacting Protein 1 Phosphorylation by Receptor Tyrosine Kinases

    PubMed Central

    Ames, Heather M.; Wang, Anmin A.; Coughran, Alanna; Evaul, Kristen; Huang, Sha; Graves, Chiron W.; Soyombo, Abigail A.

    2013-01-01

    Huntingtin-interacting protein 1 (HIP1) binds inositol lipids, clathrin, actin, and receptor tyrosine kinases (RTKs). HIP1 is elevated in many tumors, and its expression is prognostic in prostate cancer. HIP1 overexpression increases levels of the RTK epidermal growth factor receptor (EGFR) and transforms fibroblasts. Here we report that HIP1 is tyrosine phosphorylated in the presence of EGFR and platelet-derived growth factor β receptor (PDGFβR) as well as the oncogenic derivatives EGFRvIII, HIP1/PDGFβR (H/P), and TEL/PDGFβR (T/P). We identified a four-tyrosine “HIP1 phosphorylation motif” (HPM) in the N-terminal region of HIP1 that is required for phosphorylation mediated by both EGFR and PDGFβR but not by the oncoproteins H/P and T/P. We also identified a tyrosine residue (Y152) within the HPM motif of HIP1 that inhibits HIP1 tyrosine phosphorylation. The HPM tyrosines are conserved in HIP1's only known mammalian relative, HIP1-related protein (HIP1r), and are also required for HIP1r phosphorylation. Tyrosine-to-phenylalanine point mutations in the HPM of HIP1 result in proapoptotic activity, indicating that an intact HPM may be necessary for HIP1's role in cellular survival. These data suggest that phosphorylation of HIP1 by RTKs in an N-terminal region contributes to the promotion of cellular survival. PMID:23836884

  8. Plant nuclear hormone receptors: a role for small molecules in protein-protein interactions.

    PubMed

    Lumba, Shelley; Cutler, Sean; McCourt, Peter

    2010-01-01

    Plant hormones are a group of chemically diverse small molecules that direct processes ranging from growth and development to biotic and abiotic stress responses. Surprisingly, genome analyses suggest that classic animal nuclear hormone receptor homologs do not exist in plants. It now appears that plants have co-opted several protein families to perceive hormones within the nucleus. In one solution to the problem, the hormones auxin and jasmonate (JA) act as “molecular glue” that promotes protein-protein interactions between receptor F-boxes and downstream corepressor targets. In another solution, gibberellins (GAs) bind and elicit a conformational change in a novel soluble receptor family related to hormone-sensitive lipases. Abscisic acid (ABA), like GA, also acts through an allosteric mechanism involving a START-domain protein. The molecular identification of plant nuclear hormone receptors will allow comparisons with animal nuclear receptors and testing of fundamental questions about hormone function in plant development and evolution.

  9. Protein Interactions between Fe65, the LDL receptor-related protein and the amyloid precursor protein

    PubMed Central

    Mulvihill, Melinda; Guttman, Miklos; Komives, Elizabeth A.

    2011-01-01

    The adapter protein, Fe65 has been proposed to be the link between the intracellular domains of the amyloid precursor protein, APP (AICD) and the LDL receptor-related protein (LRP-CT). Functional linkage between these two proteins has been established and mutations within LRP-CT affect the amount of Aβ produced from APP. Previous work showed that the AICD binds to the protein interaction domain 2 (PID2) of Fe65. Although the structure of PID1 was solved recently all attempts to demonstrate LRP-CT binding to this domain failed. We used biophysical experiments and binding studies to investigate the binding between these three proteins. Full-length Fe65 bound more weakly to AICD than did N-terminally truncated forms, however the intramolecular domain-domain interactions that had been proposed to inhibit binding could not be observed using amide H/D exchange. Surprisingly, when the LRP-CT is phosphorylated at Tyr4507, it bound to Fe65-PID1 despite the fact that this domain belongs to the Dab-like subclass of PIDs that is not supposed to be phosphorylation dependent. Mutation of a critical arginine abolished binding providing further proof of the phosphorylation-dependence. The Fe65-PID1 domain thus provides a link between the Dab-like class and the IRS-like class of PID domains and is the first Dab-like family member to show phosphorylation-dependent binding. PMID:21650223

  10. Moonlighting Proteins and Protein–Protein Interactions as Neurotherapeutic Targets in the G Protein-Coupled Receptor Field

    PubMed Central

    Fuxe, Kjell; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Palkovits, Miklós; Tarakanov, Alexander O; Ciruela, Francisco; Agnati, Luigi F

    2014-01-01

    There is serious interest in understanding the dynamics of the receptor–receptor and receptor–protein interactions in spa hxiiyoue. tiffany taklamporce and time and their integration in GPCR heteroreceptor complexes of the CNS. Moonlighting proteins are special multifunctional proteins because they perform multiple autonomous, often unrelated, functions without partitioning into different protein domains. Moonlighting through receptor oligomerization can be operationally defined as an allosteric receptor–receptor interaction, which leads to novel functions of at least one receptor protomer. GPCR-mediated signaling is a more complicated process than previously described as every GPCR and GPCR heteroreceptor complex requires a set of G protein interacting proteins, which interacts with the receptor in an orchestrated spatio-temporal fashion. GPCR heteroreceptor complexes with allosteric receptor–receptor interactions operating through the receptor interface have become major integrative centers at the molecular level and their receptor protomers act as moonlighting proteins. The GPCR heteroreceptor complexes in the CNS have become exciting new targets for neurotherapeutics in Parkinson's disease, schizophrenia, drug addiction, and anxiety and depression opening a new field in neuropsychopharmacology. PMID:24105074

  11. Direct interactions between calcitonin-like receptor (CLR) and CGRP-receptor component protein (RCP) regulate CGRP receptor signaling.

    PubMed

    Egea, Sophie C; Dickerson, Ian M

    2012-04-01

    Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling.

  12. Direct Interactions between Calcitonin-Like Receptor (CLR) and CGRP-Receptor Component Protein (RCP) Regulate CGRP Receptor Signaling

    PubMed Central

    Egea, Sophie C.

    2012-01-01

    Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling. PMID:22315449

  13. Study of G-protein-coupled receptor-protein interactions by bioluminescence resonance energy transfer.

    PubMed

    Kroeger, Karen M; Eidne, Karin A

    2004-01-01

    Complex networks of protein-protein interactions are key determinants of cellular function, including those regulated by G-protein-coupled receptors (GPCRs). Formation of either stable or transitory complexes are involved in regulating all aspects of receptor function, from ligand binding through to signal transduction, desensitization, resensitization and downregulation. Today, 50% of all recently launched drugs are targeted against GPCRs. This particular class of proteins is extremely useful as a drug target because the receptors are partly located outside the cell, simplifying bioavailability and delivery of drugs directed against them. However, being located within the cell membrane causes difficulties for the study of GPCR function and bioluminescence resonance energy transfer (BRET), a naturally occurring phenomenon, represents a newly emerging, powerful tool with which to investigate and monitor dynamic interactions involving this receptor class. BRET is a noninvasive, highly sensitive technique, performed as a simple homogeneous assay. involving the proximity-dependent transfer of energy from an energy donor to acceptor resulting in the emission of light. This technology has several advantages over alternative approaches as the detection occurs within live cells, in real time, and is not restricted to a particular cellular compartment. The use of such biophysical techniques as BRET, will not only increase our understanding of the nature of GPCR regulation and the protein complexes involved, but could also potentially lead to the development of novel therapeutics that modulate these interactions.

  14. Computer-assisted generation of a protein-interaction database for nuclear receptors.

    PubMed

    Albert, Sylvie; Gaudan, Sylvain; Knigge, Heidrun; Raetsch, Andreas; Delgado, Asuncion; Huhse, Bettina; Kirsch, Harald; Albers, Michael; Rebholz-Schuhmann, Dietrich; Koegl, Manfred

    2003-08-01

    With the increasing amount of biological data available, automated methods for information retrieval become necessary. We employed computer-assisted text mining to retrieve all protein-protein interactions for nuclear receptors from MEDLINE in a systematic way. A dictionary of protein names and of terms denoting interactions was generated, and trioccurrences of two protein names and one interaction term in one sentence were retrieved. Abstracts containing at least one such trioccurrence were manually checked by biologists to select the relevant interactions out of the automatically extracted data. In total, 4360 abstracts were retrieved containing data on protein interactions for nuclear receptors. The resulting database contains all reported protein interactions involving nuclear receptors from 1966 to September 2001. Remarkably, the annual increase in number of reported interactors for nuclear receptors has been following an exponential growth curve in the years 1991 to 2001. Apparent in the data set is the high complexity of protein interactions for nuclear receptors. The number of interactions correlates with the number of published papers for a given receptor, suggesting that the number of reported interactors is a reflection of the intensity of research dedicated to a given receptor. Indeed, comparison of the retrieved data to a systematic yeast two-hybrid-based interaction analysis suggests that most NRs are similar with respect to the number of interacting proteins. The data set obtained serves as a source for information on NR interactions, as well as a reference data set for the improvement of advanced text-mining methods.

  15. Alcohol action on a neuronal membrane receptor: evidence for a direct interaction with the receptor protein.

    PubMed Central

    Li, C; Peoples, R W; Weight, F F

    1994-01-01

    For almost a century, alcohols have been thought to produce their effects by actions on the membrane lipids of central nervous system neurons--the well known "lipid theory" of alcohol action. The rationale for this theory is the correlation of potency with oil/water or membrane/buffer partition coefficient. Although a number of recent studies have shown that alcohols can affect the function of certain neuronal neurotransmitter receptors, there is no evidence that the alcohols interact directly with these membrane proteins. In the present study, we report that inhibition of a neuronal neurotransmitter receptor, an ATP-gated ion channel, by a series of alcohols exhibits a distinct cutoff effect. For alcohols with a molecular volume of < or = 42.2 ml/mol, potency for inhibiting ATP-activated current was correlated with lipid solubility (order of potency: 1-propanol = trifluoroethanol > monochloroethanol > ethanol > methanol). However, despite increased lipid solubility, alcohols with a molecular volume of > or = 46.1 ml/mol (1-butanol, 1-pentanol, trichloroethanol, and dichloroethanol) were without effect on the ATP-activated current. The results suggest that alcohols inhibit the function of this neurotransmitter receptor by interacting with a small hydrophobic pocket on the receptor protein. PMID:8058780

  16. 5-HT2A SEROTONIN RECEPTOR BIOLOGY: Interacting proteins, kinases and paradoxical regulation

    PubMed Central

    Roth, Bryan L

    2011-01-01

    5-hydroxytryptamine2A (5-HT2A) serotonin receptors are important pharmacological targets for a large number of central nervous system and peripheral serotonergic medications. In this review article I summarize work mainly from my lab regarding serotonin receptor anatomy, pharmacology, signaling and regulation. I highlight the role of serotonin receptor interacting proteins and the emerging paradigm of G-protein coupled receptor functional selectivity. PMID:21288474

  17. [The Cytoskelrtal Protein Zvxin Interacts with the Hedgehog Receptor Patched].

    PubMed

    Martynova, N U; Ermolina, L V; Eroshkin, F M; Zarayskiy, A G

    2015-01-01

    Earlier, we demonstrated Zyxin influence upon Hedgehog (Hh)-signaling pathway during early patterning of the central neural system (CNS) anlage of the Xenopus laevis embryo. Now we show that Zyxin can physically interact with the transmembrane receptor of Hh, Patched2 (Ptc2). Binding of Hh by this receptor activates signaling pathway, which regulates many events, including numerous types of cell differentiation during the embryonic development. In particular, patterning of the CNS anlage. The ability of Zyxin to interact with Ptc2 have been confirmed by immunoprecipitation experiments, in which we tested mutual binding affinity of Zyxin and Ptc2, as well as mutual affinity of their deletion mutants. As a result, we have established that in Xenopus levis, Zyxin binding to Ptc2 is due to the interaction of Zyxin 2nd LIM-domain (530-590 aa) with the under-membrane region of the cytoplasmic C-terminus of Ptc2 (1159-1412 aa). We have also demonstrated that similar interaction is valid for the homologous regions of the human Zyxin and human Hh receptor, Ptc1. The data obtained allow to hypothesize existence of evolutionary conserved mechanism that modulates Hh-signaling and based on the interaction of Zyxin with Ptc.

  18. Can Specific Protein-Lipid Interactions Stabilize an Active State of the Beta 2 Adrenergic Receptor?

    PubMed Central

    Neale, Chris; Herce, Henry D.; Pomès, Régis; García, Angel E.

    2015-01-01

    G-protein-coupled receptors are eukaryotic membrane proteins with broad biological and pharmacological relevance. Like all membrane-embedded proteins, their location and orientation are influenced by lipids, which can also impact protein function via specific interactions. Extensive simulations totaling 0.25 ms reveal a process in which phospholipids from the membrane’s cytosolic leaflet enter the empty G-protein binding site of an activated β2 adrenergic receptor and form salt-bridge interactions that inhibit ionic lock formation and prolong active-state residency. Simulations of the receptor embedded in an anionic membrane show increased lipid binding, providing a molecular mechanism for the experimental observation that anionic lipids can enhance receptor activity. Conservation of the arginine component of the ionic lock among Rhodopsin-like G-protein-coupled receptors suggests that intracellular lipid ingression between receptor helices H6 and H7 may be a general mechanism for active-state stabilization. PMID:26488656

  19. Muscarinic acetylcholine receptor-interacting proteins (mAChRIPs): targeting the receptorsome.

    PubMed

    Borroto-Escuela, D O; Agnati, Luigi F; Fuxe, Kjell; Ciruela, F

    2012-01-01

    Muscarinic acetylcholine receptors comprise a large family of G protein-coupled receptors that are involved in the regulation of many important functions of the central and peripheral nervous system. To achieve such a large range of physiological effects, these receptors interact with a large array of accessory proteins including scaffold molecules, ion channels and enzymes that operate as molecular transducers of muscarinic function in addition to the canonical heterotrimeric G proteins. Interestingly, as demonstrated for others G protein-coupled receptors, this type of receptor is also able to oligomerise, a fact that has been shown to play a critical role in their subcellular distribution, trafficking, and fine tuning of cholinergic signalling. On the other hand, the specificity of these receptor interactions may be largely determined by the occurrence of precise protein-interacting motifs, posttranslational modifications, and the differential tissue distribution and stoichiometry of the receptor-interacting proteins. Thus, the exhaustive cataloguing and documentation of muscarinic acetylcholine receptor-interacting proteins and the grasp of their specific function will explain key physiological differences in muscarinic-mediated cholinergic transmission. Overall, a better comprehension of the muscarinic receptor interactome will have a significant impact on the cholinergic pharmacology and thus provide previously unrealised opportunities to achieve greater specificity in muscarinic-related drug discovery and diagnostics.

  20. Quantifying the allosteric interactions within a G-protein-coupled receptor heterodimer.

    PubMed

    Zhou, Bin; Giraldo, Jesús

    2017-07-27

    G-protein-coupled receptors are central to signal transduction and cell communication. The possibility that cells use receptor heteromerization to modulate individual receptor pathways is a surmise that cannot be precluded. Given the complexity of these processes, mathematical models contribute to understanding how receptors and their respective ligands regulate signaling. Here, a mathematical model is presented that quantifies the allosteric interactions within a receptor heterodimer. The model is based on the operational model of allosterism including constitutive receptor activity, which provides the pharmacological analysis of heteromerization with well-established and widely used modeling and fitting procedures. Copyright © 2017 Elsevier Ltd. All rights reserved.

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How to Sleep In When You’re a Parent (Well, Until Six Anyway) + Giveaway

early-risingMy daughter was an early riser. Crazy early. Before the sun even dreamed of peeking over the hills, she would be wide awake, bouncing up and down in her crib like a rabbit on a pogo stick screaming, “Mommyyyyyy!!!!!” It was brutal.

I spent endless mornings, up at 4:00 a.m., sitting on the rug in the living room, my head propped up on the coffee table as I stared off into the distance in a foggy “what-the-hell-happened-to-my-life” haze. I honestly don’t know how I got through those years. I was a walking zombie.

Her early rising lasted till she was about three, and then she started “sleeping in” till 5:00 a.m. It was heaven! (It’s amazing what you consider heavenly when you’re a parent.) But our blissful slumber didn’t last long. The minute we got a reprieve from kid #1, kid #2 came along and shot it all to hell. We were thrown back into the up-all-night, early-rising life.

When #2 was about two-years-old, my husband Gabe put his foot down. “This has to stop,” he said. “They need to sleep till six.”

“Baaaaaaaa haaaaaa haaaaa,” I mocked him. “Why don’t you just tell them that?”

“I will,” Gabe said.

So he called a family meeting and told our then 2-year-old and 5-year-old that there was a new family rule. Everyone had to stay in their beds till 6 a.m. The kids made faces at him as he talked. No one was paying any attention. I sniggered in the background. Was he INSANE? I saw several problems with his new rule. The first being kids don’t know when the heck 6 a.m. is BECAUSE THEY CAN’T READ A CLOCK! You know, just a minor detail he overlooked.

When I pointed this out, Gabe looked temporarily defeated. But he’s a fighter, my man, so he refused to back down. He was sleeping till 6 a.m.if it killed him and he’d figure out a way to do it!

And shockingly, he did. The almighty Google revealed this nightlight/alarm clock thingy called the Kid’Sleep Moon. It has this cute little rabbit on it, and in one image, the rabbit is sleeping, in the other, he’s awake. If it’s nighttime, the sleeping rabbit is illuminated. If it’s time to get up, the awake rabbit is illuminated. It’s brilliant.

We bought the nightlight and it changed our lives. Seriously. We set it to 6 a.m., and you’re not going to believe this, but it worked. The kids stayed in their beds till till the bunny told them to get up every morning. Well, most mornings. It was a miracle.

Fast forward a few years, I made my “Let It Go – Mom Parody” and shot the opening sequence in front of our Kid’Sleep Moon. When the video went viral, I got an email from a lovely woman named Michelle. Her company makes the nightlight and she was so excited to see it in the video. We started chatting, and she offered to do a giveaway on the blog. So … drum roll please … it’s GIVEAWAY TIME!

One lucky person will win a Kid’Sleep Moon! Value $49.90.kids'sleep moon

a Rafflecopter giveaway

Now … the Rules:
Contest opens September 14th at 12am and closes September at 21st, at 12am PDT. You will be entered by selecting one (or more) of the options in the Rafflecopter box above! I’ll send the winner an email (so please, enter a valid email address) and announce it here and on my Facebook page. If I don’t hear back from the winner in 48 hours, the runner up will get the prize. Clear as mud? Good! Now what are you waiting for! Get entering!

*I was compensated to write this post, but if I didn’t LOVE the product and want you all to know about it, I wouldn’t have done it. I’m very picky like that.*

Related Posts:


  • 10 MORE Things I Never Thought I’d Say Before I…

  • It Gets Easier, They Lied

  • 5 Ways to Survive Your Kid’s Sleepover

  • Let It Go – Mom Parody (Video)

  • New Mom Bliss … Ha Ha Ha

Comments

  1. Ihre Artikel sind wirklich sehr interessant. Momentan suche ich Informationen für meinen Sohn (12-. Klasse Gymnasium) im Hinblick auf die später Berufs- oder Studienwahl. Können Sie mir weiterhelfen?

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  4. OMG how fun!!!! I've never been to any of those cities so I'd be thrilled to visit any. Weekend getaways are nice. My husband and I are having an overnight staycation at a hotel nearby tomorrow. It should be a fun time. It's aways nice to get out of the house. I hope you have the best time with Jon and enjoy your weekend! Can't wait to find out where y'all are going and what y'all do! Happy weekend.

    Peter Lemarc Under Din Kjol lyrics, chords, tabs

    Peter Lemarc

    Peter Lemarc Under Din Kjol lyrics, chords, tabs


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    family member to show phosphorylation-dependent binding. PMID:21650223

  5. Moonlighting Proteins and Protein–Protein Interactions as Neurotherapeutic Targets in the G Protein-Coupled Receptor Field

    PubMed Central

    Fuxe, Kjell; Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Palkovits, Miklós; Tarakanov, Alexander O; Ciruela, Francisco; Agnati, Luigi F

    2014-01-01

    There is serious interest in understanding the dynamics of the receptor–receptor and receptor–protein interactions in spa hxiiyoue. tiffany taklamporce and time and their integration in GPCR heteroreceptor complexes of the CNS. Moonlighting proteins are special multifunctional proteins because they perform multiple autonomous, often unrelated, functions without partitioning into different protein domains. Moonlighting through receptor oligomerization can be operationally defined as an allosteric receptor–receptor interaction, which leads to novel functions of at least one receptor protomer. GPCR-mediated signaling is a more complicated process than previously described as every GPCR and GPCR heteroreceptor complex requires a set of G protein interacting proteins, which interacts with the receptor in an orchestrated spatio-temporal fashion. GPCR heteroreceptor complexes with allosteric receptor–receptor interactions operating through the receptor interface have become major integrative centers at the molecular level and their receptor protomers act as moonlighting proteins. The GPCR heteroreceptor complexes in the CNS have become exciting new targets for neurotherapeutics in Parkinson's disease, schizophrenia, drug addiction, and anxiety and depression opening a new field in neuropsychopharmacology. PMID:24105074

  6. Direct interactions between calcitonin-like receptor (CLR) and CGRP-receptor component protein (RCP) regulate CGRP receptor signaling.

    PubMed

    Egea, Sophie C; Dickerson, Ian M

    2012-04-01

    Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates wxdMxdMis not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it co