Recombinant Mouse Corticotropin-releasing factor receptor 1 (Crhr1)

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Description

Molecular and Genetic Characteristics

Gene ID:

  • Mouse: 12921

  • Human: 1394 (ortholog)

  • Zebrafish: 567940 (paralog)

Protein Structure:

  • N-terminal extracellular domain (ECD) for ligand binding

  • Seven transmembrane helices (7TM) characteristic of GPCRs

  • C-terminal tail with PDZ-binding motifs (e.g., S-T-A-V sequence) for intracellular interactions

Isoforms:

  • Multiple splice variants reported, including a read-through transcript with neighboring gene MGC57346

Signaling Pathways and Mechanisms

Crhr1 primarily activates two pathways upon ligand binding:

PathwayG-Protein CouplingSecond MessengersDownstream Targets
cAMP/PKAGαs↑ cAMP, ↑ PKACREB, ERK1/2, Akt
Calcium MobilizationGαq↑ IP3, ↑ Ca²⁺PKC, Calmodulin
MAPK CascadeGαs/Gαq↑ ERK1/2 phosphorylationGene transcription regulation

Table 1: Key signaling pathways activated by Crhr1 .

  • Ligand-Dependent Internalization: CRH binding triggers receptor endocytosis, enhancing signal duration .

  • Intersectional Specificity: The Crhr1-FlpO transgenic mouse model enables precise targeting of CRHR1⁺ cells for neural and immune studies .

Neuroendocrine Regulation

  • Stress Response: Crhr1 knockout models show blunted corticosterone release under hypoxia, confirming its role in hypothalamic-pituitary-adrenal (HPA) axis activation .

  • Neurogenesis: CRHR1 signaling upregulates REST transcription factor, maintaining neural stem cell quiescence and inhibiting premature differentiation .

Immune Modulation

  • Splenic Neutrophils: LPS-induced inflammation increases Crhr1⁺ neutrophils by 17-fold, suppressing IL-1β secretion via cAMP/PKA .

  • Cell-Type Distribution in Spleen:

Cell Type% Crhr1⁺ Cells (Naive)% Crhr1⁺ Cells (Post-LPS)
Mature Neutrophils17.9 ± 246.1 ± 3.3
Granulocyte-Macrophage Precursors25.9 ± 2.914.6 ± 1.2

Table 2: Crhr1 expression dynamics in murine splenocytes .

Reproductive Physiology

  • Ovarian Function: Crhr1 is expressed in ovarian follicular cells, suggesting roles in sexual maturation and steroidogenesis .

Technical Considerations

  • Antagonist Sensitivity: CP154,526 blocks CRHR1-mediated Pomc upregulation under hypoxia .

  • Transgenic Models:

    • Crhr1-FlpO mice enable intersectional manipulation of CRHR1⁺ neurons using Flp-dependent viral vectors .

    • GFP-reporter strains validate endogenous Crhr1 expression patterns in the CNS .

Product Specs

Form
Lyophilized powder
Note: We will prioritize shipping the format currently in stock. However, if you have any specific format requirements, please indicate them during order placement, and we will fulfill your request.
Lead Time
Delivery time may vary depending on the purchasing method or location. Please consult your local distributors for specific delivery time information.
Note: All of our proteins are standardly shipped with normal blue ice packs. If you require dry ice shipping, please inform us in advance as additional fees will apply.
Notes
Repeated freezing and thawing is not recommended. Store working aliquots at 4°C for up to one week.
Reconstitution
We recommend briefly centrifuging this vial before opening to ensure the contents settle to the bottom. Reconstitute the protein in deionized sterile water to a concentration of 0.1-1.0 mg/mL. We recommend adding 5-50% glycerol (final concentration) and aliquoting for long-term storage at -20°C/-80°C. Our default final glycerol concentration is 50%, which can be used as a reference.
Shelf Life
Shelf life is influenced by various factors including storage conditions, buffer composition, storage temperature, and the inherent stability of the protein.
Generally, the shelf life of liquid form is 6 months at -20°C/-80°C. Lyophilized form has a shelf life of 12 months at -20°C/-80°C.
Storage Condition
Store at -20°C/-80°C upon receipt. Aliquoting is necessary for multiple uses. Avoid repeated freeze-thaw cycles.
Tag Info
Tag type will be determined during the manufacturing process.
The tag type will be determined during the production process. If you have a specific tag type requirement, please inform us, and we will prioritize developing the specified tag.
Synonyms
Crhr1; Crhr; Corticotropin-releasing factor receptor 1; CRF-R-1; CRF-R1; CRFR-1; Corticotropin-releasing hormone receptor 1; CRH-R-1; CRH-R1
Buffer Before Lyophilization
Tris/PBS-based buffer, 6% Trehalose.
Datasheet
Please contact us to get it.
Expression Region
24-415
Protein Length
Full Length of Mature Protein
Species
Mus musculus (Mouse)
Target Names
Target Protein Sequence
SLQDQQCESLSLASNVSGLQCNASVDLIGTCWPRSPAGQLVVRPCPAFFYGVRYNTTNNG YRECLANGSWAARVNYSECQEILNEEKKSKVHYHIAVIINYLGHCISLVALLVAFVLFLR LRSIRCLRNIIHWNLISAFILRNATWFVVQLTVSPEVHQSNVAWCRLVTAAYNYFHVTNF FWMFGEGCYLHTAIVLTYSTDRLRKWMFVCIGWGVPFPIIVAWAIGKLYYDNEKCWFGKR PGVYTDYIYQGPMILVLLINFIFLFNIVRILMTKLRASTTSETIQYRKAVKATLVLLPLL GITYMLFFVNPGEDEVSRVVFIYFNSFLESFQGFFVSVFYCFLNSEVRSAIRKRWRRWQD KHSIRARVARAMSIPTSPTRVSFHSIKQSTAV
Uniprot No.

Target Background

Function
Corticotropin-releasing factor receptor 1 (Crhr1) is a G-protein coupled receptor that binds corticotropin-releasing factor (CRH) and urocortin (UCN). It exhibits high affinity for both ligands. Ligand binding induces a conformational change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors, such as adenylate cyclase. This activation promotes the stimulation of adenylate cyclase, leading to increased intracellular cAMP levels. Additionally, Crhr1 inhibits the activity of the calcium channel CACNA1H. Crhr1 is essential for normal embryonic development of the adrenal gland and for proper hormonal responses to stress. It plays a significant role in mediating responses to anxiogenic stimuli.
Gene References Into Functions
  1. Expression of Crhr1 is reduced in the pituitary gland of corticotropin-releasing hormone knock-out mice subjected to repeated stress. PMID: 28993972
  2. CRF-R1 expression levels correlated with the severity of DSS-induced colitis. Activation of CRF-R1 exacerbated inflammation, while inhibition of CRF-R1 mitigated inflammation, as assessed by the DAI and histological scores in the colon samples of DSS-treated mice. PMID: 29115460
  3. A sexually dimorphic expression of CRFR1 was observed within the rostral portion of the anteroventral periventricular nucleus of the hypothalamus. PMID: 28823817
  4. These findings revealed a prominent role for CRF1 signaling in mast cells as a positive modulator of stimuli-induced degranulation. PMID: 28684600
  5. A switch in G protein coupling for type 1 corticotropin-releasing factor receptors promotes excitability in epileptic brains. PMID: 27303056
  6. The study characterized the influences of early-life stress on the developmental trajectory of hippocampal pyramidal neurons, highlighting the critical role of CRHR1 in modulating these negative outcomes evoked by early-life stress. PMID: 26792004
  7. The beneficial effects of CRFR1 antagonism observed in transgenic mice may be mechanistically linked to the modulation of oxidative stress pathways. PMID: 28750017
  8. The study found that corticotropin-releasing factor type 1 receptor within the paraventricular nucleus of the hypothalamus is a crucial central component of hypothalamic-pituitary-adrenal axis regulation, preparing the organism for successive exposure to stressful stimuli. PMID: 28135239
  9. The study demonstrated that CRF1 receptor-deficiency prolongs, whereas CRF2 receptor-deficiency shortens, the duration of recognition memory deficits induced by morphine discontinuation, revealing contrasting roles for the two known CRF receptor subtypes in cognitive dysfunction associated with opiate withdrawal. PMID: 26907806
  10. Crhr1, in a subset of AgRP neurons, plays a regulatory role that enables appropriate sympathetic nervous system activation, thereby protecting the organism from hypothermia and hypoglycemia. PMID: 27211900
  11. The cyclic AMP (cAMP) response of CRHR1 in physiologically relevant scenarios engages separate cAMP sources, involving the atypical soluble adenylyl cyclase (sAC) in addition to transmembrane adenylyl cyclases (tmACs). PMID: 27402953
  12. A role was found for extra-hypothalamic CRF-R1 in stress-escalated alcohol drinking. PMID: 26576941
  13. This study demonstrated an anatomical mechanism for sex-differences in the convergent modulation of ventrolateral medulla catecholaminergic neurons by CRF and glutamate. PMID: 26306872
  14. These results indicate that the NPS-NPSR system may regulate locomotion alongside the CRF1 system in the substantia nigra. PMID: 26239581
  15. Bladder smooth muscle contractility remains unchanged by CsA; however, there are alterations in the levels of the downstream transcription factors MEF-2 and NFAT. PMID: 26052002
  16. Genetic disruption of the CRF1R pathway decreased the period of extinction in both males and females, suggesting that CRF/CRF1R is involved in the duration of aversive memory. PMID: 25830629
  17. Anatomical and biochemical findings demonstrate that accumulation of Abeta is significantly reduced in the brain of Alzheimer's disease model mice lacking CRFR1, providing support for a direct relationship between CRFR1 and Abeta production pathways. PMID: 25697705
  18. Results reveal the influences of early postnatal stress on the development of medial prefrontal cortex (mPFC) pyramidal neurons, highlighting CRF1 as a key molecule in modulating the detrimental stress effects on the structural organizations of mPFC. PMID: 25403725
  19. This study aimed to investigate the cellular localization of CRF and UCNs in the ileum and explore whether and how this cellular expression is altered in conditions of intestinal Schistosoma mansoni-induced inflammation. PMID: 25358399
  20. NPY and PYY are necessary for CRF1 modulation of feeding behavior during stress. PMID: 25238483
  21. The data supports a critical involvement of Crhr1 in environmentally-induced anxiolysis. PMID: 24840018
  22. Sympathetic activity induced by naloxone-precipitated morphine withdrawal is blocked in genetically engineered mice lacking functional CRF1 receptor. PMID: 25582704
  23. Crhr1 in the basolateral amygdala is critically involved as a plasticity gene in the bidirectional epigenetic rescue of extremes in trait anxiety. PMID: 24518397
  24. CRHR1 has a proinflammatory and therefore a protumorigenesis effect in terms of colitis associated cancer, which may be beneficial for developing new therapeutic approaches for inflammation and cancer prevention and treatment. PMID: 25015995
  25. cPLA2 participates in CRHR1-induced apoptosis and CRHR2-inhibited apoptosis. PMID: 24776847
  26. CRFR1 signaling in the ventral tegmental area presents a target for convergent effects of both cue- and stress-induced cocaine-seeking pathways. PMID: 25164654
  27. Data suggest that the gene x stress exposure interaction is based on naturally occurring genetic variations in the Crhr1 gene associated with enhanced CRHR1-mediated signaling. PMID: 24773341
  28. Leptin regulates corticotropin-releasing factor and urocortin 2/3 mRNA in hypothalamic neurons. PMID: 24083959
  29. Altered CRF1 receptor-mediated signaling in the ventral tegmental area promotes binge-like alcohol consumption in mice. PMID: 23763790
  30. Blockade of CRF1 receptors does not exert specific effects on ethanol intake in an animal model of binge drinking. PMID: 23398267
  31. CRFR1 plays crucial roles in whole body energy homeostasis. PMID: 24054833
  32. This study demonstrated that Expression of CRFR1 and Glu5R mRNA in different brain areas following repeated testing in mice that differ in habituation behaviour. PMID: 23458743
  33. ERK1/2 activation in response to CRH is biphasic, involving a first cAMP- and B-Raf-dependent early phase and a second phase that critically depends on CRHR1 internalization and beta-arrestin2. PMID: 23371389
  34. Studies show that SAP97 interactions with CRFR1 attenuate CRFR1 endocytosis and that SAP97 is involved in coupling G protein-coupled receptors to the activation of the ERK1/2 signaling pathway. PMID: 23576434
  35. The CRH-CRHR1 system interacts with the nectin-afadin complex to mediate the effects of stress on memory and structural plasticity. PMID: 23644483
  36. CRHR1 agonism stimulates rat and mouse fetal testis steroidogenesis. PMID: 23133512
  37. Reductions in anxiety and corticosteroid levels conferred by heterozygosity of CRF receptor type-1 do not improve a deficit in working memory observed in APP/hAbeta/PS1 mice. PMID: 22336193
  38. Corticotropin-releasing hormone (CRH) and its type 1 receptor (CRHR1) play a central role in coordinating the endocrine, autonomic, and behavioral responses to stress. PMID: 22886732
  39. The findings highlight the importance of forebrain CRHR1 in modulating some of the anxiogenic effects of early-life stress. PMID: 22672268
  40. CRHR1 does not have a role in basal alcohol intake or relapse-like drinking situations with a low stress load. PMID: 22113086
  41. Data show that CRFR1 and CRFR2 double-KO mice did not exhibit repeated stress-induced alterations in tau-P or solubility. PMID: 22451915
  42. Our data reveal a novel anxiolytic role for CRFR1 in the globus pallidus external. PMID: 22131403
  43. Data suggest that corticotropin-releasing factor receptor types 1 and 2 mediation of stress-induced hippocampal tau phosphorylation may be limited to emotional stressors. PMID: 21722209
  44. Results suggest that forebrain CRF1 is crucial for the programming of cognitive function by early-life stress. PMID: 21940453
  45. Present results are suggestive that CRF1 (but not CRF2) receptors play a crucial role in the anxiogenic and antinociceptive effects induced by CRF in the dorsal periaqueductal gray in mice. PMID: 21723867
  46. CRH-R1 inhibition is not protective against pneumococcal disease induced by stress. PMID: 21774994
  47. Results define a bidirectional model for the role of CRHR1 in anxiety and suggest that an imbalance between CRHR1-controlled anxiogenic glutamatergic and anxiolytic dopaminergic systems might lead to emotional disorders. PMID: 21885734
  48. Forebrain CRHR1 deficiency prevented the down-regulation of hippocampal glucocorticoid receptor expression by chronic stress but induced increased body weight gain during persistent stress exposure. PMID: 21296667
  49. Data show that stress has opposing effects on CRHR1 and CRHR2 neuronal systems, suggesting that regulation of the relative contribution of the two CRH receptors to brain CRH pathways may be essential in coordinating physiological responses to stress. PMID: 19302188
  50. This study presented a VSDI assay for the investigation of neuronal activity propagation through the hippocampus and demonstrates that CRH, via CRHR1. PMID: 20619419

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Database Links

KEGG: mmu:12921

STRING: 10090.ENSMUSP00000091455

UniGene: Mm.1892

Protein Families
G-protein coupled receptor 2 family
Subcellular Location
Cell membrane; Multi-pass membrane protein. Endosome.
Tissue Specificity
Detected in brain cortex (at protein level).

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