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
Multiple splice variants reported, including a read-through transcript with neighboring gene MGC57346
Crhr1 primarily activates two pathways upon ligand binding:
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 .
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 .
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 Neutrophils | 17.9 ± 2 | 46.1 ± 3.3 |
| Granulocyte-Macrophage Precursors | 25.9 ± 2.9 | 14.6 ± 1.2 |
Table 2: Crhr1 expression dynamics in murine splenocytes .
Ovarian Function: Crhr1 is expressed in ovarian follicular cells, suggesting roles in sexual maturation and steroidogenesis .