Affinage

RAMP1

Receptor activity-modifying protein 1 · UniProt O60894

Length
148 aa
Mass
17.0 kDa
Annotated
2026-04-28
61 papers in source corpus 27 papers cited in narrative 27 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

RAMP1 is a single-pass transmembrane accessory protein that heterodimerizes with calcitonin receptor-like receptor (CLR/CRLR) to constitute a functional CGRP receptor, governing receptor trafficking, ligand specificity, and downstream signaling. Expressed alone, RAMP1 is retained as a disulfide-linked homodimer in the ER; upon 1:1 heterodimerization with CLR, it escorts the receptor to the cell surface, where it confers CGRP selectivity over adrenomedullin and enables Gs-coupled cAMP production as well as β-arrestin recruitment and clathrin-mediated internalization of the intact CRLR–RAMP1–β-arrestin complex (PMID:10342881, PMID:11535606, PMID:17503773). Key extracellular residues—Trp74, Trp84, Y66, H97—form the binding interface for both CGRP peptide agonists and small-molecule antagonists (gepants), while C-mannosylation at Trp56 stabilizes RAMP1 protein without affecting surface trafficking (PMID:19914210, PMID:20188075, PMID:35942636). Beyond classical CGRP receptor pharmacology, RAMP1 transduces nociceptor-derived CGRP signals in macrophages, goblet cells, T lymphocytes, hepatic stellate cells, and dental pulp stem cells, regulating mucosal barrier protection, inflammation-induced lymphangiogenesis, liver regeneration and fibrosis, and tissue repair through downstream YAP/TAZ, TGFβ1/Smad2, and ERK/MAPK pathways (PMID:36243004, PMID:32329113, PMID:39103072, PMID:38451947).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 1999 High

    The central question of how a single GPCR (CRLR) discriminates between CGRP and adrenomedullin was resolved by showing that RAMP1 coexpression switches CRLR pharmacology to CGRP selectivity, establishing RAMP1 as a ligand-specificity determinant.

    Evidence Radioligand binding and cAMP reporter assays with RAMP1/RAMP2 coexpression in COS-7 and UMR-106 cells

    PMID:10342881

    Open questions at the time
    • Structural basis of specificity switching unknown
    • Whether RAMP1 contacts the ligand directly was not tested
  2. 2001 High

    The question of how RAMP1 reaches the cell surface and what happens to the complex after agonist stimulation was answered: RAMP1 alone is ER-retained as a homodimer, forms a 1:1 heterodimer with CRLR for surface trafficking, and CGRP stimulation triggers dynamin- and β-arrestin-dependent internalization of the intact ternary complex.

    Evidence Subcellular fractionation, non-reducing SDS-PAGE, co-IP, dominant-negative dynamin/β-arrestin constructs, confocal imaging

    PMID:11535606

    Open questions at the time
    • Post-endocytic fate of the complex (recycling vs. degradation) not determined
    • Phosphorylation sites on CLR driving internalization not mapped
  3. 2007 High

    Whether RAMP1 is required for CLR to engage any downstream effector was demonstrated in living cells: BRET titration showed selective CRLR–RAMP1 heterodimerization and that CRLR alone cannot recruit G proteins or β-arrestin.

    Evidence BRET with Rluc/GFP fusions, radioligand binding, cAMP assays in living cells

    PMID:17503773

    Open questions at the time
    • Which G protein subtypes RAMP1 enables was not dissected
    • Whether RAMP1 allosterically activates CLR or merely chaperones it remained unclear
  4. 2006 Medium

    The three-dimensional arrangement of the RAMP1 extracellular domain—three disulfide bonds and three α-helices—was established, predicting CLR-binding and ligand-contact residues that guided subsequent mutagenesis.

    Evidence Cysteine mutagenesis combined with ab initio structure prediction and MD simulation in COS-7 cells

    PMID:16632510

    Open questions at the time
    • Full structure was computational, not experimentally determined at atomic resolution
    • Predicted interface residues required functional validation
  5. 2009 High

    Systematic alanine scanning and chimera analysis mapped the RAMP1 extracellular domain into distinct functional modules: Y66/H97 for CLR trafficking, L69/T73/P85/N86/F101 for CGRP recognition, and helix 1 plus residues 62–69 for receptor association, separating trafficking from signaling determinants.

    Evidence Alanine-scanning mutagenesis, RAMP1–RAMP3 chimeras, cell-surface ELISA and cAMP assays in Cos7 cells

    PMID:19072332 PMID:20017504

    Open questions at the time
    • Atomic-resolution contacts between RAMP1 and CLR not yet visualized
    • Whether these residues affect biased signaling was untested
  6. 2009 High

    How small-molecule antagonists (gepants) interact with the CLR–RAMP1 interface was revealed: Trp74 of RAMP1 and Met42 of CLR are critical contacts for olcegepant and telcagepant, establishing that gepants exploit the heterodimer interface rather than binding CLR alone.

    Evidence Site-directed mutagenesis of CLR and RAMP1, radioligand binding with quantitative affinity measurements for two clinical antagonists

    PMID:19914210 PMID:20188075

    Open questions at the time
    • No co-crystal structure of gepant bound to the CLR–RAMP1 complex
    • Whether newer gepants (e.g., rimegepant, ubrogepant) share the same binding mode was not tested
  7. 2014 High

    The first in vivo loss-of-function evidence showed RAMP1 promotes airway inflammation: RAMP1-KO mice had reduced airway resistance in an asthma model, and cell-specific CLR deletion excluded smooth muscle, pointing to endothelial/inflammatory cells as the relevant RAMP1-dependent compartment.

    Evidence RAMP1 global KO and cell-specific CLR KO mice, ovalbumin sensitization, methacholine challenge

    PMID:25010197

    Open questions at the time
    • Specific immune cell type mediating the effect not identified
    • Downstream signaling pathway in airway inflammation not dissected
  8. 2019 High

    RAMP1 was placed in neuroimmune circuits beyond classical sensory neuron biology: in Kupffer cells it restrains pro-inflammatory cytokine production during hepatitis, and in bone marrow it supports hematopoietic repopulation under proliferative stress by limiting ROS and apoptosis.

    Evidence RAMP1-KO mice with Kupffer cell/T cell depletion and adoptive transfer (hepatitis); BM transplantation repopulation and ROS assays (hematopoiesis)

    PMID:30462657 PMID:30674976

    Open questions at the time
    • Whether RAMP1-dependent anti-inflammatory signaling in Kupffer cells is Gs/cAMP-mediated was not shown
    • Mechanism linking RAMP1 to ROS regulation in HSCs not defined
  9. 2020 High

    RAMP1-dependent CGRP signaling was connected to the Hippo pathway effector YAP: RAMP1 deficiency causes YAP hyperphosphorylation (inactivation), impairing liver regeneration, while CGRP treatment stabilizes YAP in hepatocytes; separately, RAMP1 in CD4+ T cells drives VEGF-C/D-dependent lymphangiogenesis.

    Evidence RAMP1-KO mice with partial hepatectomy and CCl4 injury; CGRP stimulation of human hepatocytes; LPS-induced lymphangiogenesis with CD4+ cell depletion

    PMID:31911634 PMID:32329113

    Open questions at the time
    • How CGRP/Gs signaling inhibits LATS kinase-mediated YAP phosphorylation is unknown
    • Whether lymphangiogenic and hepatoprotective roles share common downstream pathways not tested
  10. 2022 High

    A direct nociceptor–epithelial signaling axis was established: nociceptor-derived CGRP acts on RAMP1 in intestinal goblet cells to trigger mucus secretion and protect against colitis, defining RAMP1 as a mucosal barrier regulator.

    Evidence Nociceptor ablation, chemogenetic activation, epithelial-specific Ramp1 conditional KO, CGRP rescue in colitis model

    PMID:36243004

    Open questions at the time
    • Intracellular signaling pathway from RAMP1/CLR to mucin granule exocytosis in goblet cells not identified
    • Whether RAMP1 regulates other secretory epithelial cells not tested
  11. 2022 Medium

    C-mannosylation at Trp56 was identified as a post-translational modification that stabilizes RAMP1 protein and promotes cell migration, without affecting CLR surface trafficking, adding a new regulatory layer to RAMP1 biology.

    Evidence Mass spectrometry, Trp56 mutagenesis, protein stability and cell migration assays

    PMID:35942636

    Open questions at the time
    • Enzyme responsible for C-mannosylation not identified
    • Whether this modification is regulated in physiological or pathological contexts unknown
  12. 2024 High

    RAMP1 was positioned in multiple new tissue-repair and disease contexts: it mediates macrophage dysfunction in endometriosis, constrains Type 17 immunity via CD8+ T cells in skin, promotes dental pulp stem cell migration for tissue repair, modulates hepatic fibrosis through TGFβ1/Smad2 and YAP, and protects against ischemia-reperfusion injury by restraining ERK/MAPK and YAP phosphorylation.

    Evidence Endometriosis mouse model with macrophage phenotyping; intravital imaging of T cell–nerve interactions; scRNA-seq and denervation in dental pulp; RAMP1-KO fibrosis and IR models with pharmacological rescue

    PMID:38451947 PMID:38638379 PMID:39103072 PMID:39196292 PMID:39504351

    Open questions at the time
    • Whether RAMP1 signals through CLR vs. CTR (AMY1R) in each cell type is often assumed but not formally tested
    • Biased signaling contributions (Gs vs. β-arrestin) in tissue-specific outcomes undefined
    • Relative contributions of CGRP vs. amylin as endogenous ligands in non-neuronal tissues unclear
  13. 2025 Medium

    RAMP1 expression in trigeminal ganglia is hormonally regulated—estrogen upregulates Ramp1 via ERβ—and RAMP1 is required for estrous-cycle-dependent fluctuations in the broader CGRP system, providing a molecular basis for sex differences in migraine.

    Evidence RT-qPCR across estrous stages, estrogen/progesterone administration, Ramp1-KO mice of both sexes

    PMID:40528180

    Open questions at the time
    • Direct ERβ binding to the Ramp1 promoter not demonstrated
    • Whether hormonal regulation of RAMP1 extends to peripheral tissues is unknown
    • Functional consequence for migraine-relevant trigeminovascular signaling not directly tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) how CGRP–RAMP1/CLR signaling mechanistically connects to YAP/Hippo pathway regulation, (2) whether RAMP1 pairs with CLR vs. CTR in each of the newly identified non-neuronal cell types, and (3) how biased agonism (Gs vs. β-arrestin) at the RAMP1-containing receptor contributes to divergent tissue-specific outcomes.
  • No structural basis for RAMP1-mediated biased signaling
  • RAMP1 partner receptor identity in macrophages, goblet cells, T cells, and stellate cells not systematically determined
  • Endogenous ligand hierarchy (CGRP vs. amylin vs. adrenomedullin) at RAMP1-containing receptors in non-neuronal tissues unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 4 GO:0098772 molecular function regulator activity 4 GO:0048018 receptor ligand activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005783 endoplasmic reticulum 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 4
Partners
ARRB1ARRB2CALCRCALCRLNKX3.1YAP1
Complex memberships
CLR–RAMP1 (CGRP receptor)CTR–RAMP1 (AMY1 receptor)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 RAMP1 acts as a determinant of ligand specificity for the calcitonin receptor-like receptor (CRLR): coexpression of RAMP1 with CRLR generates a functional CGRP receptor (Gs-coupled), whereas RAMP2 coexpression yields an adrenomedullin receptor. RAMP1 competitively inhibits RAMP2-evoked ADM receptor expression, shifting receptor pharmacology to CGRP selectivity. Radioligand binding ([125I]hαCGRP, [125I]rADM), cAMP-responsive luciferase reporter assay, transient transfection in COS-7 and UMR-106 cells Endocrinology High 10342881
2001 RAMP1 expressed alone is retained intracellularly in the ER and Golgi as a disulfide-linked homodimer. Upon coexpression with CRLR, RAMP1 forms a 1:1 heterodimer that traffics to the cell surface; heterodimer formation promotes intramolecular disulfide bonds within RAMP1 but does not involve intermolecular disulfide bonds between the two partners. CGRP stimulation leads to CRLR phosphorylation and dynamin- and β-arrestin-dependent internalization of the CRLR–RAMP1 complex as a stable ternary complex with β-arrestin via clathrin-coated pits. Subcellular fractionation, non-reducing SDS-PAGE, co-immunoprecipitation, dominant-negative dynamin and β-arrestin constructs, confocal immunofluorescence The Journal of biological chemistry High 11535606
2007 BRET titration experiments in living cells demonstrated that CRLR and RAMP1 selectively form heterodimers; both proteins can also independently form homodimers. RAMP1 is required for CRLR to engage G proteins and β-arrestin upon CGRP stimulation—CRLR alone cannot recruit these signaling partners. Bioluminescence resonance energy transfer (BRET) with Rluc/GFP fusion proteins, radioligand binding, cAMP production assay Biochemistry High 17503773
2006 Ab initio structural modeling of the RAMP1 extracellular domain determined the disulfide bond arrangement (Cys27–Cys82, Cys40–Cys72, Cys57–Cys104) by site-directed mutagenesis, and identified three α-helices (residues 29–51, 60–80, 87–100). The model predicted Phe93, Tyr100, Phe101 as a CLR-binding interface and Trp74, Phe92 as ligand-interaction residues. Site-directed mutagenesis of cysteines, ab initio structure prediction with molecular dynamics refinement, functional expression in COS-7 cells Biophysical journal Medium 16632510
2009 Alanine mutagenesis across the RAMP1 N-terminal extracellular domain identified Y66 and H97 as critical for CLR trafficking (receptor association), while L69, T73, and residues in helix 3 (P85, N86, F101) contribute to CGRP recognition and cAMP signaling. M48 had a modest effect on CLR surface delivery. Alanine-scanning mutagenesis of 22 RAMP1 residues, cell-surface ELISA, cAMP assay in Cos7 cells Biochemistry High 19072332
2009 Non-peptide CGRP receptor antagonists BIBN4096BS (olcegepant) and MK-0974 (telcagepant) interact with the CLR–RAMP1 interface: Trp-74 of RAMP1 is a key contact for both antagonists (W74K mutation reduces BIBN4096BS affinity >300-fold and MK-0974 affinity similarly), and Met-42 of CLR N-terminal domain is critical (M42A reduces BIBN4096BS affinity 48-fold, MK-0974 ~900-fold). Site-directed mutagenesis of CLR (residues 23–63) and RAMP1 (W74K), radioligand binding and functional assays Biochemical and biophysical research communications High 19914210
2010 RAMP1 Trp-84 is critical for high-affinity binding of both non-peptide antagonists (telcagepant, olcegepant) and the peptide agonists CGRP and CGRP(8-37); Arg-67 of RAMP1 is selectively important for telcagepant but not the BIBN4096BS analog, indicating distinct but overlapping binding modes within the RAMP1 extracellular domain. Alanine replacement mutagenesis of RAMP1 residues, radioligand binding, functional cAMP assay in Cos7 cells Biochemical and biophysical research communications High 20188075
2010 RAMP1–RAMP3 chimera analysis showed that helix 1 of RAMP1 and residues 62–69 of helix 2 are required for CLR trafficking (association), while residues 86–89 of RAMP1 helix 3 contribute to peptide (αCGRP, adrenomedullin) potency without affecting βCGRP, and residues 90–94 have dual roles in CLR recognition and CGRP binding. RAMP1–RAMP3 chimera construction, CLR trafficking assay (cell-surface ELISA), agonist-stimulated cAMP assay in Cos7 cells Biochemistry High 20017504
2011 Position 74 of RAMP1 (Trp74) governs differential peptide pharmacology: substitutions alter AM potency at the CGRP receptor (CLR/RAMP1) differently from RAMP3 position 74 (Glu74), confirming this position as a determinant of ligand discrimination between adrenomedullin and CGRP at their respective receptors. Site-directed mutagenesis of position 74 in RAMP1 and RAMP3 with multiple amino acid substitutions, cAMP assay in Cos7 cells, cell-surface ELISA Peptides Medium 21402116
2013 RAMP1 overexpression in MG-63 osteoblast-like cells increases CRLR surface expression and enhances CGRP-induced osteogenic differentiation (alkaline phosphatase activity, collagen I expression, mineralization), demonstrating RAMP1's role in promoting CRLR membrane localization and amplifying CGRP-mediated osteoblast differentiation. Stable transfection with RAMP1 eukaryotic expression vector, RT-PCR, Western blot, immunofluorescence, ALP activity assay, Alizarin Red staining Journal of cellular biochemistry Medium 22949393
2013 NKX3.1 transcription factor directly represses RAMP1 gene expression in prostate cells; RAMP1 knockdown reduces prostate cancer cell proliferation and tumorigenicity in vitro and in vivo, and decreases MEK1 expression and ERK1/2 phosphorylation, placing RAMP1 upstream of the MAPK signaling pathway in prostate cancer. ChIP-seq (NKX3.1 binding to RAMP1 locus), shRNA knockdown, gene expression profiling, xenograft tumor models, Western blot for pERK1/2 The American journal of pathology High 23867798
2014 RAMP1-deficient mice show reduced airway resistance and airway inflammation in an ovalbumin-sensitized asthma model; loss of CLR from smooth muscle cells did not affect airway resistance, indicating CGRP signaling through RAMP1/CLR promotes asthma pathology via endothelial and inflammatory cells rather than smooth muscle. RAMP1 knockout mouse (exon 3 deletion), cell-specific CLR knockout, methacholine challenge, airway resistance measurement, histological assessment of inflammation PloS one High 25010197
2018 Photoaffinity cross-linking using unnatural amino acid (p-azido-L-phenylalanine) incorporated into CLR ECL2 identified key contacts between CGRP and the transmembrane domain of CLR: I284 (ECL2) and L291 (top of TM5) are the main contacts, with minor contacts at M223 (TM3) and F349 (TM6), consistent with CGRP sitting atop the TM bundle of the CLR–RAMP1 complex. Genetic code expansion with unnatural amino acid mutagenesis, photoaffinity cross-linking, fluorescein-labeled CGRP analogue, molecular modeling Biochemistry High 30004692
2019 RAMP1 in Kupffer cells (liver-resident macrophages) is required for restraining cytokine production during immune-mediated hepatitis; RAMP1-deficient mice show exacerbated ConA-induced liver injury with increased pro-inflammatory cytokines; co-culture experiments showed RAMP1-dependent crosstalk between Kupffer cells and splenic T cells amplifies cytokine expression. RAMP1 knockout mice, Kupffer cell depletion, T cell depletion, splenectomy, adoptive transfer of splenic T cells, in vitro co-culture with cytokine measurement PloS one High 30462657
2019 RAMP1 signaling is required for stress-induced hematopoietic repopulation; RAMP1-deficient bone marrow has decreased repopulation capacity with enhanced ROS production and apoptosis under proliferative stress, while steady-state hematopoiesis is maintained. Continuous CGRP exposure reduces BM immature hematopoietic cell numbers via CRLR/RAMP1. RAMP1 knockout mice, bone marrow transplantation repopulation assay, ROS measurement, apoptosis assays, chronic CGRP administration Scientific reports Medium 30674976
2020 RAMP1 deficiency impairs liver regeneration after partial hepatectomy and CCl4 injury; mechanistically, RAMP1 loss leads to hyperphosphorylation of YAP on Ser127 and Ser397 (inactivating modifications), reducing YAP/TAZ protein levels and suppressing YAP-controlled cell cycle regulators. CGRP treatment of liver slice cultures and primary human hepatocytes increased YAP protein and reduced its phosphorylation. RAMP1 knockout mice, 70% partial hepatectomy model, CCl4 chronic injury model, Western blot for pYAP, in vitro CGRP stimulation of human/mouse liver slices and primary hepatocytes FASEB journal High 32329113
2020 RAMP1 signaling in immune cells (specifically CD4+ T cells) promotes inflammation-induced lymphangiogenesis by driving VEGF-C and VEGF-D expression; RAMP1-deficient macrophages display a pro-inflammatory M1 phenotype shift, impairing lymphatic vessel growth. RAMP1 knockout mice, LPS-induced peritoneal lymphangiogenesis model, CD4+ cell depletion, immunohistochemistry, qRT-PCR for VEGF-C/D Laboratory investigation Medium 31911634
2022 Intestinal goblet cells express RAMP1, which mediates CGRP signaling from Nav1.8+ nociceptor neurons to drive rapid goblet cell emptying and mucus secretion. Loss of epithelial RAMP1 increases susceptibility to colitis; CGRP administration rescues nociceptor-ablated mice from colitis, establishing a direct nociceptor–goblet cell axis requiring RAMP1. Mouse nociceptor ablation, chemogenetic nociceptor activation, epithelial Ramp1 conditional KO, mucus thickness measurement, colitis model, CGRP administration rescue experiments Cell High 36243004
2022 RAMP1 undergoes C-mannosylation at Trp56, a modification that enhances RAMP1 protein stability and promotes cell migration activity, but does not affect RAMP1 trafficking to the plasma membrane with CLR. Mass spectrometry identification of C-mannosylation, mutagenesis of Trp56, protein stability assays, cell migration assays The FEBS journal Medium 35942636
2024 CGRP–RAMP1 signaling in macrophages promotes a pro-endometriosis phenotype: CGRP stimulation impairs macrophage efferocytosis and supports endometrial cell growth in a RAMP1-dependent manner. In vivo blockade of CGRP–RAMP1 reduces mechanical hyperalgesia, spontaneous pain, and lesion size in a mouse endometriosis model. Human endometriosis samples, nonsurgical mouse model, nociceptor ablation, in vitro macrophage phenotyping with efferocytosis assays, RAMP1-dependent cell growth assays, pharmacological CGRP blockade in vivo Science translational medicine High 39504351
2024 CGRP–RAMP1 signaling between commensal-specific CD8+ T cells and somatosensory neurons constrains Type 17 immune responses in the skin; RAMP1 upregulation in commensal-induced T cells was observed by intravital imaging, and CGRP–RAMP1 signaling moderated T cell activation and influenced wound healing outcomes. Intravital imaging (T cell proximity to cutaneous nerve fibers), flow cytometry (RAMP1 expression on T cells), commensal colonization model, wound healing assay Proceedings of the National Academy of Sciences of the United States of America High 38451947
2024 RAMP1 absence exacerbates liver fibrosis; mechanistically, RAMP1 deficiency impairs TGFβ1/Smad2 signaling and reduces YAP activity in liver parenchyma. In vitro, CGRP stimulation of hepatic stellate cells (LX-2) induces TGFβ1 production, downstream Smad2 signaling, α-SMA expression, collagen synthesis, and YAP nuclear translocation. RAMP1 KO murine fibrosis model, Western blot for Smad2 phosphorylation and YAP, in vitro CGRP stimulation of LX-2 cells, immunofluorescence for YAP localization Experimental cell research Medium 39103072
2024 RAMP1 protects hepatocytes against ischemia-reperfusion injury by inhibiting ERK/MAPK pathway activation and YAP phosphorylation; RAMP1-KO mice show increased ERK phosphorylation and YAP Ser phosphorylation, promoting apoptosis. ERK inhibitor (SCH772984) and YAP phosphorylation inhibitor (PY-60) reduced apoptosis in RAMP1-KO settings. RAMP1 KO mouse liver ischemia-reperfusion model, Western blot for pERK and pYAP, pharmacological inhibition experiments in vitro and in vivo Journal of clinical and translational hepatology Medium 38638379
2024 Sensory nerve-derived CGRP binds RAMP1 on dental pulp stem cells (DPSCs) to promote collective migration to injury sites, facilitating pulp repair. Sensory denervation impaired DPSC recruitment and caused ectopic mineralization; exogenous CGRP rescue and BIBN4096 antagonism confirmed RAMP1 dependence. In vivo denervation, single-cell RNA-seq, immunohistochemistry, indirect co-culture with conditioned medium from trigeminal neurons, CGRP protein and BIBN4096 treatment, collective migration assays Cellular and molecular life sciences Medium 39196292
2024 Amylin receptor AMY1R (CTR+RAMP1) exhibits a basal subunit equilibrium favoring free CTR and free RAMP1; rat amylin and αCGRP agonists promote CTR–RAMP1 subunit association, and these changes in heterodimer assembly directly determine cAMP signaling phenotype. Novel biochemical assay resolving AMYR heterodimers vs free subunits, live cell membrane experiments, G protein coupling and cAMP signaling assays bioRxivpreprint Medium bio_10.1101_2024.10.09.617487
2025 CGRP/RAMP1 signaling mediates the increase (but not the decrease) in CSD-evoked calcium signaling in a subset of meningeal macrophages, as shown by intravital two-photon imaging in reporter mice with pharmacological CGRP receptor blockade. Chronic intravital two-photon calcium imaging (Pf4Cre:GCaMP6s mice), cortical spreading depolarization induction, pharmacological CGRP/RAMP1 blockade bioRxivpreprint Medium bio_10.1101_2025.10.01.679335
2025 RAMP1 expression in the trigeminal ganglion varies across the estrous cycle (peaks in proestrus, declines in diestrus), inversely correlating with Calca (CGRPα); estrogen upregulates Ramp1 expression in both sexes via ERβ-dependent mechanisms. In Ramp1 KO mice, cyclical variation of Calca, Ramp2, and Ramp3 is absent and basal Calca is elevated in males, demonstrating RAMP1 is required for hormonal regulation of the CGRP system. RT-qPCR across estrous cycle stages, estrogen/progesterone administration, Ramp1 KO mice (both sexes), correlation analysis with Esr2 The journal of headache and pain Medium 40528180

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2008 Calcitonin receptor-like receptor (CLR), receptor activity-modifying protein 1 (RAMP1), and calcitonin gene-related peptide (CGRP) immunoreactivity in the rat trigeminovascular system: differences between peripheral and central CGRP receptor distribution. The Journal of comparative neurology 267 18186028
2022 Nociceptor neurons direct goblet cells via a CGRP-RAMP1 axis to drive mucus production and gut barrier protection. Cell 181 36243004
1999 A receptor activity modifying protein (RAMP)2-dependent adrenomedullin receptor is a calcitonin gene-related peptide receptor when coexpressed with human RAMP1. Endocrinology 142 10342881
2001 Agonist-promoted internalization of a ternary complex between calcitonin receptor-like receptor, receptor activity-modifying protein 1 (RAMP1), and beta-arrestin. The Journal of biological chemistry 114 11535606
2025 Nociceptive neurons promote gastric tumour progression via a CGRP-RAMP1 axis. Nature 67 39972142
2010 Cerebellar distribution of calcitonin gene-related peptide (CGRP) and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) in rat. Molecular and cellular neurosciences 66 21040789
2002 Increased myocardial expression of RAMP1 and RAMP3 in rats with chronic heart failure. Biochemical and biophysical research communications 55 12051717
2005 Antiapoptotic effect of calcitonin gene-related peptide on oxidative stress-induced injury in H9c2 cardiomyocytes via the RAMP1/CRLR complex. Journal of molecular and cellular cardiology 51 16242145
2014 Deficiency of RAMP1 attenuates antigen-induced airway hyperresponsiveness in mice. PloS one 40 25010197
2000 Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells. Biochemical and biophysical research communications 40 10772950
2007 Assembly and signaling of CRLR and RAMP1 complexes assessed by BRET. Biochemistry 38 17503773
2012 Deficiency of the CGRP receptor component RAMP1 attenuates immunosuppression during the early phase of septic peritonitis. Immunobiology 37 22656887
2009 Non-peptidic antagonists of the CGRP receptor, BIBN4096BS and MK-0974, interact with the calcitonin receptor-like receptor via methionine-42 and RAMP1 via tryptophan-74. Biochemical and biophysical research communications 35 19914210
2019 RAMP1 and RAMP3 Differentially Control Amylin's Effects on Food Intake, Glucose and Energy Balance in Male and Female Mice. Neuroscience 34 31881259
2010 Mapping the CGRP receptor ligand binding domain: tryptophan-84 of RAMP1 is critical for agonist and antagonist binding. Biochemical and biophysical research communications 34 20188075
2020 RAMP1 signaling in immune cells regulates inflammation-associated lymphangiogenesis. Laboratory investigation; a journal of technical methods and pathology 33 31911634
2015 DNA methylation of RAMP1 gene in migraine: an exploratory analysis. The journal of headache and pain 32 26501962
2024 The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota. Proceedings of the National Academy of Sciences of the United States of America 28 38451947
2024 Nociceptor-to-macrophage communication through CGRP/RAMP1 signaling drives endometriosis-associated pain and lesion growth in mice. Science translational medicine 28 39504351
2012 Localization of calcitonin receptor-like receptor (CLR) and receptor activity-modifying protein 1 (RAMP1) in human gastrointestinal tract. Peptides 28 22484227
2017 RAMP1 signaling improves lymphedema and promotes lymphangiogenesis in mice. The Journal of surgical research 26 29078910
2019 Targeting the CALCB/RAMP1 axis inhibits growth of Ewing sarcoma. Cell death & disease 25 30741933
2017 RAMP1 suppresses mucosal injury from dextran sodium sulfate-induced colitis in mice. Journal of gastroenterology and hepatology 24 27513455
2020 The CGRP receptor component RAMP1 links sensory innervation with YAP activity in the regenerating liver. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 23 32329113
2010 Involvement of vascular endothelial growth factor signaling in CLR/RAMP1 and CLR/RAMP2-mediated pro-angiogenic effect of intermedin on human vascular endothelial cells. International journal of molecular medicine 23 20596610
2009 Structure-function analysis of RAMP1 by alanine mutagenesis. Biochemistry 23 19072332
2017 Distribution of CGRP and its receptor components CLR and RAMP1 in the rat retina. Experimental eye research 22 28603014
2013 RAMP1 is a direct NKX3.1 target gene up-regulated in prostate cancer that promotes tumorigenesis. The American journal of pathology 22 23867798
2011 Structure-function analysis of amino acid 74 of human RAMP1 and RAMP3 and its role in peptide interactions with adrenomedullin and calcitonin gene-related peptide receptors. Peptides 22 21402116
2018 Photoaffinity Cross-Linking and Unnatural Amino Acid Mutagenesis Reveal Insights into Calcitonin Gene-Related Peptide Binding to the Calcitonin Receptor-like Receptor/Receptor Activity-Modifying Protein 1 (CLR/RAMP1) Complex. Biochemistry 20 30004692
2012 Association study of the calcitonin gene-related polypeptide-alpha (CALCA) and the receptor activity modifying 1 (RAMP1) genes with migraine. Gene 20 23237777
2018 RAMP1 in Kupffer cells is a critical regulator in immune-mediated hepatitis. PloS one 17 30462657
2015 Association of RAMP1 rs7590387 with the risk of migraine transformation into medication overuse headache. Headache 17 25881990
2006 Aldosterone increases RAMP1 expression in mesenteric arteries from spontaneously hypertensive rats. Regulatory peptides 17 16458982
2006 Characterization of the structure of RAMP1 by mutagenesis and molecular modeling. Biophysical journal 16 16632510
2019 CGRP-CRLR/RAMP1 signal is important for stress-induced hematopoiesis. Scientific reports 15 30674976
2021 Differential Synovial CGRP/RAMP1 Expression in Men and Women With Knee Osteoarthritis. Cureus 14 34109089
2013 The influence of RAMP1 overexpression on CGRP-induced osteogenic differentiation in MG-63 cells in vitro: an experimental study. Journal of cellular biochemistry 13 22949393
2022 Characterization of Antibodies against Receptor Activity-Modifying Protein 1 (RAMP1): A Cautionary Tale. International journal of molecular sciences 10 36555690
2025 RAMP1-dependent hormonal regulation of CGRP and its receptor in the trigeminal ganglion. The journal of headache and pain 9 40528180
2024 Deletion of RAMP1 Signaling Enhances Diet-induced Obesity and Fat Absorption via Intestinal Lacteals in Mice. In vivo (Athens, Greece) 9 38148085
2023 Body weight lowering effect of glucose-dependent insulinotropic polypeptide and glucagon-like peptide receptor agonists is more efficient in RAMP1/3 KO than in WT mice. European journal of pharmacology 9 37454968
2019 The neuropeptide receptor subunit RAMP1 constrains the innate immune response during acute pancreatitis in mice. Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 9 31109903
2011 Suppression of ovalbumin-induced allergic diarrhea by diminished intestinal peristalsis in RAMP1-deficient mice. Biochemical and biophysical research communications 8 21683059
2022 A High Methylation Level of a Novel -284 bp CpG Island in the RAMP1 Gene Promoter Is Potentially Associated with Migraine in Women. Brain sciences 7 35624913
2021 Molecular simulations reveal the impact of RAMP1 on ligand binding and dynamics of calcitonin gene-related peptide receptor (CGRPR) heterodimer. Computers in biology and medicine 7 34923287
2024 RAMP1 Signaling Mitigates Acute Lung Injury by Distinctively Regulating Alveolar and Monocyte-Derived Macrophages. International journal of molecular sciences 6 39337592
2010 Structure-function analysis of RAMP1-RAMP3 chimeras. Biochemistry 6 20017504
2022 C-mannosylation regulates stabilization of RAMP1 protein and RAMP1-mediated cell migration. The FEBS journal 5 35942636
2024 Signalling of the neuropeptide calcitonin gene-related peptide (CGRP) through RAMP1 promotes liver fibrosis via TGFβ1/Smad2 and YAP pathways. Experimental cell research 4 39103072
2024 Sensory nerves drive migration of dental pulp stem cells via the CGRP-Ramp1 axis in pulp repair. Cellular and molecular life sciences : CMLS 4 39196292
2024 Involvement of RAMP1/p38MAPK signaling pathway in osteoblast differentiation in response to mechanical stimulation: a preliminary study. Journal of orthopaedic surgery and research 3 38825686
2023 The neuroimmune CGRP-RAMP1 axis tunes cutaneous adaptive immunity to the microbiota. bioRxiv : the preprint server for biology 3 38234748
2024 Nociceptive neurons interact directly with gastric cancer cells via a CGRP/Ramp1 axis to promote tumor progression. bioRxiv : the preprint server for biology 2 38496544
2024 RAMP1 Protects Hepatocytes against Ischemia-reperfusion Injury by Inhibiting the ERK/YAP Pathway. Journal of clinical and translational hepatology 2 38638379
2025 Intra-tumoural RAMP1+ B cells promote resistance to neoadjuvant anti-PD-1-based therapy in oesophageal squamous cell carcinoma. Immunotherapy advances 1 40385640
2025 Sensory neuropeptide CGRP and its co-receptor RAMP1 drive tumour cell growth in gastrointestinal cancers. BMJ oncology 1 41158750
2025 Acupuncture accelerates wound healing via CGRP-RAMP1-TSP1-mediated macrophage M2 polarization. Chinese medicine 1 41250153
2025 Oxidative stress impairs the expansion of regulatory T cells in active vitiligo via dysregulated CGRP-RAMP1-Gαi3 signaling. Free radical biology & medicine 1 41453541
2024 Spinal RAMP1-mediated neuropathic pain sensitisation in the aged mice through the modulation of CGRP-CRLR pain signalling. Heliyon 1 39224276
2024 Lack of RAMP1 Signaling Suppresses Liver Regeneration and Angiogenesis Following Partial Hepatectomy in Mice. In vivo (Athens, Greece) 0 39187322