Affinage

CALCRL

Calcitonin gene-related peptide type 1 receptor · UniProt Q16602

Length
461 aa
Mass
53.0 kDa
Annotated
2026-06-09
47 papers in source corpus 22 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CALCRL (CRLR/CLR) is a class B GPCR that signals only as an obligate heterodimer with a receptor activity-modifying protein (RAMP), and the identity of the bound RAMP determines ligand selectivity: CRLR/RAMP1 constitutes a CGRP receptor, whereas CRLR/RAMP2 and CRLR/RAMP3 form adrenomedullin receptors that elevate cAMP (PMID:10217420, PMID:10781016). The CRLR/RAMP1 complex couples to G proteins and β-arrestin upon CGRP stimulation, and BRET in living cells shows that CRLR and RAMP1 selectively associate as cell-surface heterodimers; a RAMP1 trafficking-defective mutant still heterodimerizes with CRLR, establishing that surface delivery depends on complex conformation rather than on heterodimerization per se (PMID:17503773). Receptor maturation and ligand engagement require post-translational modification: N-glycosylation of CRLR at Asn123 is essential for ligand binding and signaling (PMID:11389975), and the RAMP partner contributes its own glycosylation- and disulfide-dependent folding, with RAMP1 reaching the surface only through CRLR pairing because it lacks the N-glycans that allow RAMP2/RAMP3 to traffic independently (PMID:11854283, PMID:12939163). Through this system CALCRL transduces vascular and cytoprotective signaling: it mediates adrenomedullin-driven endothelial migration, invasion and tube formation cooperatively with VEGF (PMID:14712479), drives eNOS-dependent NO production, proliferation and angiogenesis under transcriptional control of a shear-stress HSF1 enhancer (PMID:38602103), and the CLR/RAMP1 heterodimer mediates the hypotensive responses to both CGRP and adrenomedullin in vivo (PMID:27940069). CRLR expression is induced by hypoxia, both transcriptionally via an HIF-1α-responsive element in its promoter (PMID:12824306) and post-transcriptionally with rapid protein accumulation (PMID:15567147). In disease, the ADM/CGRP–CALCRL axis sustains acute myeloid leukemia: CALCRL is required for leukemic colony formation and engraftment (PMID:31182782), drives cell-cycle progression, DNA repair and mitochondrial OxPHOS through E2F1/BCL2 to maintain leukemic stem cells and chemoresistance (PMID:33462236), and confers daunorubicin resistance via an XRCC5/PDK1/AKT axis (PMID:37948318). CALCRL signaling is also cytoprotective in cardiomyoblasts and alveolar cells and defines spinal projection neurons that amplify mechanical itch (PMID:16242145, PMID:38695251, PMID:41248150).

Mechanistic history

Synthesis pass · year-by-year structured walk · 22 steps
  1. 1999 High

    Established that CRLR is not an orphan receptor but acquires defined ligand pharmacology only when paired with a RAMP, identifying the RAMP2/CRLR complex as a functional adrenomedullin receptor.

    Evidence Heterologous co-expression with cAMP assays in HeLa and 293 cells plus endogenous expression in vascular cells

    PMID:10217420

    Open questions at the time
    • Did not resolve the structural basis of RAMP-conferred selectivity
    • Other RAMP/CRLR combinations not tested in this study
  2. 2000 High

    Defined the combinatorial logic that the bound RAMP dictates whether CRLR is a CGRP receptor (RAMP1) or an adrenomedullin receptor (RAMP2/3), linking receptor phenotype to tissue RAMP expression.

    Evidence Co-transfection radioligand binding in HEK293 and quantitative mRNA correlation across rat tissues

    PMID:10781016

    Open questions at the time
    • Functional consequences in native tissues inferred from correlation, not perturbation
  3. 2001 High

    Identified Asn123 N-glycosylation of CRLR as a requirement for ligand binding and signaling, defining a post-translational determinant of receptor competence independent of RAMP identity.

    Evidence Site-directed mutagenesis (N66Q/N118Q/N123Q), radioligand binding, cAMP and FACS surface assays in HEK293 and CHO cells

    PMID:11389975

    Open questions at the time
    • Mechanism by which Asn123 glycan supports binding vs folding not separated
    • Glycan structure not characterized
  4. 2001 Medium

    Demonstrated in a physiologically relevant cardiomyocyte context that AM responsiveness requires CRLR/RAMP2 co-expression, validating the heterodimer model in native cells.

    Evidence CRE-luciferase reporter, CRLR antisense, and CGRP(8-37) antagonism in neonatal rat cardiomyocytes

    PMID:11754972

    Open questions at the time
    • Reporter and antisense readouts only; no direct surface complex measurement
    • Single lab
  5. 2002 High

    Reframed RAMP function away from a simple chaperone model, showing RAMP1 surface delivery depends on heterodimerization with CRLR because it lacks the N-glycans that allow RAMP2/3 to traffic independently.

    Evidence Xenopus oocyte reconstitution with quantitative surface binding and engineered RAMP1 glycosylation mutants

    PMID:11854283

    Open questions at the time
    • Trafficking machinery interpreting glycan signals not identified
  6. 2003 High

    Extended the maturation requirements to the RAMP subunit, showing RAMP3 glycosylation and conserved disulfide bonds are needed for a functional CRLR/RAMP3 adrenomedullin receptor.

    Evidence Oocyte expression with systematic RAMP3 glycosylation/cysteine mutagenesis and [125I]AM binding

    PMID:12939163

    Open questions at the time
    • Disulfide connectivity not directly mapped
    • Generalization to RAMP1/RAMP2 not tested here
  7. 2003 High

    Connected CRLR expression to oxygen sensing by identifying a functional HIF-1α hypoxia response element in the human promoter, explaining selective CRLR (not RAMP) induction under hypoxia.

    Evidence Promoter cloning, HRE mutagenesis, luciferase reporter and RT-PCR in primary microvascular endothelial cells

    PMID:12824306

    Open questions at the time
    • Downstream physiological consequence of CRLR induction not measured in this study
  8. 2004 Medium

    Established a direct angiogenic role for CALCRL receptors, showing AM drives endothelial migration, invasion and tube formation via CRLR/RAMP2 and CRLR/RAMP3 and cooperates with VEGF.

    Evidence Migration, invasion, Matrigel cord and blocking-antibody assays in HUVEC

    PMID:14712479

    Open questions at the time
    • Intracellular effectors of the angiogenic response not defined
    • Single lab
  9. 2005 Medium

    Showed RAMP1/CRLR signaling is cytoprotective, with CGRP suppressing oxidative-stress apoptosis through Bcl-2/Bax modulation in a RAMP1-specific manner.

    Evidence Viability, annexin V, caspase-3, DNA fragmentation and RT-PCR with CGRP(8-37) antagonism in H9c2 cells

    PMID:16242145

    Open questions at the time
    • Signaling pathway linking receptor to Bcl-2/Bax not delineated
    • Single lab
  10. 2005 Medium

    Revealed a post-transcriptional layer of hypoxic CRLR regulation, with acute hypoxia raising CRLR protein before mRNA, complementing the HIF-1α transcriptional mechanism.

    Evidence Parallel RT-PCR and Western blot in CASMC and chronic hypoxia rat ventricle

    PMID:15567147

    Open questions at the time
    • Post-transcriptional mechanism (translation vs stability) not identified
    • Single lab
  11. 2007 High

    Provided direct biophysical evidence for selective cell-surface heterodimerization and showed signaling output (G protein and β-arrestin engagement) requires RAMP1, separating heterodimer formation from trafficking competence.

    Evidence BRET titration, radioligand binding, cAMP and biosensor assays in living cells with a trafficking-defective RAMP1 mutant

    PMID:17503773

    Open questions at the time
    • Conformational change driving trafficking not structurally defined
    • Homodimer functional relevance unclear
  12. 2016 High

    Assigned in vivo physiological responsibility, showing the CLR/RAMP1 heterodimer is the principal mediator of AM- and CGRP-induced hypotension with RAMP2/3 contributions.

    Evidence Multiple Ramp and Calcrl knockout mouse lines with intravenous peptide challenge and blood pressure measurement

    PMID:27940069

    Open questions at the time
    • Mechanistic basis of sex-dependent basal blood pressure differences unexplained
  13. 2019 Medium

    Identified CALCRL as a driver of acute myeloid leukemia, required for colony formation and correlated with leukemic engraftment capacity.

    Evidence CRISPR-Cas9 knockout, colony assays and patient-derived xenograft engraftment

    PMID:31182782

    Open questions at the time
    • Downstream pathway not yet defined in this study
    • Single lab
  14. 2019 Medium

    Demonstrated that CGRP–CALCRL/RAMP1 signaling protects AML cells from cytostatic apoptosis and sustains leukemic stem cell properties, nominating it as a therapeutic target.

    Evidence CALCRL expression analysis, olcegepant antagonism and an AML mouse model with stem-cell and apoptosis readouts

    PMID:31756985

    Open questions at the time
    • Transcriptional/metabolic effectors not yet mapped here
    • Single lab
  15. 2019 Medium

    Showed the same CGRP-CALCRL/RAMP1 axis maintains normal stress hematopoiesis, distinguishing stress-dependent from steady-state requirements.

    Evidence Ramp1-/- mice with bone marrow transplantation, proliferation, apoptosis and ROS assays

    PMID:30674976

    Open questions at the time
    • Whether the protective program overlaps with the leukemic program untested
    • Single lab
  16. 2019 Medium

    Linked the RAMP2/CRLR-cAMP axis to neuronal survival, with RAMP2 mutants disrupting signaling and Ramp2 haploinsufficiency causing retinal ganglion cell death.

    Evidence Exome sequencing, RAMP2 mutant transfection with cAMP assays and a heterozygous Ramp2 knockout mouse

    PMID:31000793

    Open questions at the time
    • Causal mutation-to-phenotype chain in patients not fully established
    • Single lab
  17. 2020 High

    Provided an atomic-resolution view of the CLR–RAMP1 interface, showing the therapeutic antibody erenumab wedges into the subunit interface to block ligand binding and explain receptor selectivity.

    Evidence X-ray crystallography of the erenumab–CGRPR complex with functional validation

    PMID:32049005

    Open questions at the time
    • Full agonist-bound active-state structure not resolved here
  18. 2021 High

    Defined the mechanistic program by which ADM-CALCRL sustains leukemic stem cells, coupling the receptor to E2F1/BCL2-dependent cell cycle, DNA repair and OxPHOS and to chemoresistance.

    Evidence shRNA/siRNA knockdown, PDX models with in vivo cytarabine, transcriptomics and metabolic assays

    PMID:33462236

    Open questions at the time
    • Direct receptor-to-E2F1 signaling steps not fully reconstructed
  19. 2023 Medium

    Identified an additional drug-resistance effector arm, with CALCRL upregulating XRCC5/PDK1 and AKT/PKCε phosphorylation to confer daunorubicin resistance, reversible by XRCC5 knockdown.

    Evidence CALCRL overexpression and XRCC5 siRNA rescue with viability, apoptosis, cell-cycle assays and xenografts in HL-60/Molm-13 cells

    PMID:37948318

    Open questions at the time
    • How receptor signaling induces XRCC5 not defined
    • Single lab
  20. 2024 High

    Mapped the endothelial transcriptional control and functional output of CALCRL, showing an HSF1-bound shear-stress enhancer drives expression that supports eNOS/NO, proliferation and angiogenesis.

    Evidence CRISPR enhancer deletion, HSF1 ChIP/EMSA, ATAC-seq, reporter assays and CALCRL knockdown functional readouts

    PMID:38602103

    Open questions at the time
    • Causal contribution of the rs880890 variant in vivo not established
  21. 2024 Medium

    Showed CGRP-CALCRL/CGRPR signaling couples to TRPV1-mediated Ca2+ entry via PLC/PKC to protect alveolar cells from hyperoxic injury.

    Evidence Calcium imaging, patch clamp, TRPV1 siRNA and pharmacological inhibition in A549 cells under hyperoxia

    PMID:38695251

    Open questions at the time
    • Physical coupling between receptor and TRPV1 not demonstrated
    • Single lab
  22. 2025 Medium

    Defined a neuronal sensory role for Calcrl-expressing spinal projection neurons in amplifying mechanical itch through altered excitability and synaptic balance.

    Evidence Chemogenetic gain/loss-of-function, electrophysiology and behavioral assays in chronic itch mouse models

    PMID:41248150

    Open questions at the time
    • Role of CGRP ligand and RAMP partner in these neurons not addressed
    • Single lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the diverse downstream programs (vascular eNOS/angiogenesis, leukemic E2F1/BCL2 and XRCC5/AKT, neuronal TRPV1 and itch) are selected from a common CRLR/RAMP cAMP-G protein-β-arrestin core remains unresolved.
  • No unified map linking receptor-proximal signaling to cell-type-specific effectors
  • Active-state agonist-bound receptor structure not available
  • Whether leukemic and protective hematopoietic programs are mechanistically distinct is untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2 GO:0060090 molecular adaptor activity 1
Localization
GO:0005886 plasma membrane 3
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 3
Partners
RAMP1RAMP2RAMP3
Complex memberships
Adrenomedullin receptor (CRLR/RAMP2)Adrenomedullin receptor (CRLR/RAMP3)CGRP receptor (CRLR/RAMP1)

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 The RAMP2/CRLR complex functions as a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells, mediating cAMP elevation upon adrenomedullin stimulation when both RAMP2 and CRLR are co-expressed. Heterologous co-expression in HeLa EBNA and 293 EBNA cells; cAMP assay; RT-PCR of endogenous expression FEBS letters High 10217420
2000 Rat CRLR co-transfected with RAMP1 cDNA specifies a CGRP receptor, while co-transfection with RAMP2 or RAMP3 specifies an adrenomedullin receptor in HEK293 cells; CGRP binding in rat tissues correlates with RAMP1 mRNA levels and total binding correlates with CRLR mRNA levels. Co-transfection in HEK293 cells; radioligand binding; quantitative mRNA correlation across eight rat tissues British journal of pharmacology High 10781016
2002 CRLR does not require heterodimerization with RAMPs for efficient cell surface expression in Xenopus oocytes; RAMP2 and RAMP3 require N-glycosylation for plasma membrane targeting; RAMP1 (not N-glycosylated) reaches the cell surface only upon heterodimer formation with CRLR; introduction of N-glycosylation sites into RAMP1 allows RAMP1 cell surface expression independent of CRLR. These data argue against a chaperone function for RAMPs. Xenopus oocyte expression system; quantitative cell surface binding assay; site-directed mutagenesis of N-glycosylation sites in RAMP1 The Journal of biological chemistry High 11854283
2001 Glycosylation of CRLR at Asn123 is required for ligand binding and signal transduction; mutation of Asn123 (but not Asn66 or Asn118) abolishes adrenomedullin/CGRP binding and signaling and reduces cell surface expression; blocking all N-glycosylation with tunicamycin abolishes ligand binding regardless of which RAMP is co-expressed. Site-directed mutagenesis of CRLR N-glycosylation sites (N66Q, N118Q, N123Q); radioligand binding in HEK293 EBNA and CHO-K1 cells; cAMP signaling assay; FACS cell surface expression analysis Biochimica et biophysica acta High 11389975
2001 CRLR and RAMP2 co-expression is required for functional adrenomedullin (AM) signaling in rat cardiomyocytes; overexpression of either CRLR or RAMP2 alone potentiates AM-stimulated CRE-luciferase activity, with co-overexpression producing an additive ~4-fold increase; AM signaling is abolished by the antagonist CGRP(8-37) or by CRLR antisense. Transient transfection with CRE-luciferase reporter in neonatal rat cardiomyocytes; CRLR antisense; receptor antagonist treatment; RT-PCR Peptides Medium 11754972
2003 The human CRLR gene promoter contains an HIF-1alpha-responsive hypoxia response element (HRE); mutation of the HRE abolishes hypoxia-induced promoter activation; hypoxia transcriptionally upregulates CRLR mRNA in microvascular endothelial cells, while RAMP1, RAMP2, and RAMP3 expression is unaffected by hypoxia. 5'-RACE; promoter cloning; luciferase reporter assay in primary microvascular endothelial cells; HRE site-directed mutagenesis; semi-quantitative RT-PCR FASEB journal High 12824306
2003 N-glycosylation of RAMP3 (at two to four of four consensus sites) and disulfide bonds formed by all six conserved cysteine residues are required for functional CRLR/RAMP3 adrenomedullin receptor expression; elimination of all N-glycans significantly reduces [125I]AM binding and increases EC50; mutation of all six cysteines abolishes adrenomedullin binding completely. Xenopus oocyte expression system; mutagenesis of N-glycosylation sites and cysteine residues in RAMP3; [125I]AM radioligand binding; EC50 determination Biochemistry High 12939163
2005 CGRP exerts antiapoptotic effects on H9c2 cardiomyoblasts under oxidative stress specifically via the RAMP1/CRLR complex: CGRP prevents caspase-3 activation, phosphatidylserine externalization, DNA fragmentation, and Bax upregulation, increases Bcl-2 expression; these effects are blocked by the RAMP1/RAMP2 inhibitor CGRP(8-37) but not mimicked by adrenomedullin (a RAMP2 agonist), indicating RAMP1/CRLR specificity. MTT cell viability; annexin V/propidium iodide flow cytometry; caspase-3 activity assay; DNA fragmentation; RT-PCR for Bcl-2/Bax; dot blotting; pharmacological antagonism with CGRP(8-37) Journal of molecular and cellular cardiology Medium 16242145
2007 CRLR and RAMP1 selectively associate as heterodimers at the cell surface in living cells; CRLR and RAMP1 can also independently form homodimers; CRLR engages G proteins and β-arrestin following CGRP stimulation only in the presence of RAMP1; a RAMP1 mutant unable to reach the cell surface still heterodimerizes with CRLR, indicating that deficient targeting results from altered complex conformation rather than impaired heterodimerization. BRET (bioluminescence resonance energy transfer) titration in living cells; radioligand binding; cAMP production assay; BRET with G protein and β-arrestin biosensors Biochemistry High 17503773
2004 AM promotes HUVEC migration, invasion, and differentiation into cord-like structures via CRLR/RAMP2 and CRLR/RAMP3 receptors; suboptimal concentrations of VEGF and AM act synergistically; AM-induced capillary tube formation is not blocked by anti-VEGF antibodies, indicating AM does not act indirectly through VEGF upregulation. Migration and invasion assays; Matrigel cord formation assay; blocking antibody experiments; cAMP assay in HUVEC International journal of cancer Medium 14712479
2016 The hypotensive response to AM is primarily mediated through the CLR/RAMP1 heterodimer in vivo; CGRP's hypotensive activity is predominantly through CLR/RAMP1; CLR/RAMP2 and CLR/RAMP3 also contribute to AM-mediated hypotension; Calcrl+/- mice show attenuated hypotensive response to AM and sex-dependent differences in basal blood pressure. Genetic mouse models (Ramp1-/-, Ramp2+/-, Ramp3-/-, double KO, Calcrl+/-); intravenous injection of AM or CGRP; blood pressure measurement under anesthesia Peptides High 27940069
2020 Crystal structure of erenumab (anti-CGRPR monoclonal antibody) in complex with CGRPR reveals that erenumab's 21-residue CDR-H3 loop projects into the deep interface between the CLR and RAMP1 subunits of CGRPR, directly blocking ligand binding; erenumab engages residues specific to both CLR and RAMP1, providing the molecular basis for receptor selectivity. X-ray crystallography of erenumab–CGRPR complex; functional binding validation Cell reports High 32049005
2019 CGRP acting through CALCRL/RAMP1 protects AML cells from apoptosis induced by cytostatic drugs; specific CGRP antagonists block this protective effect; CGRP/CALCRL promotes leukemic stem cell properties; the CGRP antagonist olcegepant increases differentiation and reduces leukemic burden in a mouse model of AML. CALCRL expression analysis in AML cell lines and primary samples; pharmacological inhibition with olcegepant; C57BL/6 AML mouse model; apoptosis assays; flow cytometry for stem cell markers International journal of molecular sciences Medium 31756985
2021 The ADM-CALCRL axis drives cell cycle progression, DNA repair, and mitochondrial OxPHOS function in AML blasts dependent on E2F1 and BCL2 signaling; CALCRL knockdown impairs leukemic growth, decreases LSC frequency, and sensitizes to cytarabine in patient-derived xenograft models; CALCRL depletion reduces LSC frequency of relapse-initiating cells post-chemotherapy in vivo. shRNA/siRNA CALCRL knockdown; patient-derived xenograft (PDX) models; in vivo cytarabine treatment; transcriptomic analysis identifying E2F1 and BCL2 dependence; cell cycle and mitochondrial function assays Nature communications High 33462236
2019 CRISPR-Cas9-mediated knockout of CALCRL significantly impairs colony formation in human myeloid leukemia cell lines; CALCRL levels positively correlate with leukemic engraftment capacity of primary patient samples in immunocompromised mice. CRISPR-Cas9 knockout; colony formation assay; patient-derived xenograft engraftment assay Leukemia Medium 31182782
2019 CGRP-CALCRL/RAMP1 signaling is important for maintaining hematopoiesis under proliferative stress: Ramp1-/- mice show decreased bone marrow repopulation capacity and low proliferation with enhanced ROS production and apoptosis following transplantation stress; steady-state hematopoiesis is largely maintained in Ramp1-/- mice. Ramp1-/- mouse model; bone marrow transplantation assay; cell proliferation and apoptosis assays; ROS measurement Scientific reports Medium 30674976
2019 Mutant RAMP2 proteins aggregate in transfected cells and disrupt the AM-RAMP2/CRLR-cAMP signaling pathway; ablation of one Ramp2 allele in mice leads to cAMP reduction and retinal ganglion cell death, establishing that the RAMP2/CRLR-cAMP axis is required for retinal ganglion cell survival. Exome sequencing; functional transfection studies with RAMP2 mutants; heterozygous Ramp2 knockout mouse model; cAMP measurement; retinal ganglion cell survival assay Genetics in medicine Medium 31000793
2005 Acute hypoxia in coronary artery smooth muscle cells (CASMC) rapidly increases CRLR protein level (~3.5-fold within 1 hour) independently of changes in CRLR mRNA, indicating a major post-transcriptional regulatory mechanism; later mRNA elevation was also observed; chronic hypoxia in rat ventricles upregulates both mRNA and protein levels of CRLR and all three RAMPs. RT-PCR for mRNA; Western blotting for protein; in vitro CASMC hypoxia model; in vivo chronic hypobaric hypoxia rat model Biochemical and biophysical research communications Medium 15567147
2024 CALCRL mediates eNOS, APLN (apelin), angiopoietin, prostaglandin, and EDN1 (endothelin-1) signaling pathways in endothelial cells; HSF1 binds a shear stress-responsive enhancer harboring rs880890 to regulate CALCRL transcription; CRISPR deletion of this enhancer downregulates CALCRL expression; CALCRL knockdown decreases endothelial cell proliferation, tube formation, and NO production. CRISPR enhancer deletion; HSF1 siRNA knockdown; chromatin immunoprecipitation (ChIP-qPCR); ATAC-seq; luciferase reporter assay; electromobility shift assay (EMSA); CALCRL siRNA knockdown with functional readouts (proliferation, tube formation, NO production) Arteriosclerosis, thrombosis, and vascular biology High 38602103
2023 CALCRL overexpression in AML cells confers resistance to daunorubicin, reduces DNA damage and G0/G1 cell cycle arrest, and reduces apoptosis; mechanistically, CALCRL overexpression upregulates XRCC5 and PDK1 expression and increases AKT/PKCε phosphorylation; XRCC5 siRNA knockdown in CALCRL-overexpressing cells restores drug sensitivity and reverses downstream AKT/PKCε phosphorylation. CALCRL overexpression constructs in HL-60 and Molm-13 cells; XRCC5 siRNA; RT-PCR; Western blot; cell viability, apoptosis, cell cycle assays; in vivo xenograft mouse model Anti-cancer drugs Medium 37948318
2025 Spinal Calcrl+ neurons function as projection neurons that amplify mechanical itch signaling; in chronic itch models, these neurons show enhanced intrinsic excitability, increased Aβ-fiber-evoked excitatory synaptic input, and reduced inhibitory input; chemogenetic activation of Calcrl+ neurons induces mechanical itch sensitization in naïve mice, while chemogenetic inhibition alleviates it in chronic itch models. Chemogenetic manipulation (DREADD); behavioral itch assays; electrophysiology (synaptic recordings); morphological assays; chronic itch mouse models (allergic contact dermatitis, atopic dermatitis, psoriasis) PloS one Medium 41248150
2024 CGRP acting via CALCRL/CGRPR protects alveolar cells from hyperoxia-induced injury by inducing Ca2+ entry through TRPV1 channels; CGRP enhances non-selective membrane currents through TRPV1; CGRP-induced Ca2+ increase is reduced by inhibiting the PLC/PKC pathway; selective inhibitors of CGRPR or TRPV1 attenuate CGRP-mediated cell proliferation and anti-apoptotic effects. Digital calcium imaging; patch clamp electrophysiology; TRPV1 siRNA knockdown; pharmacological inhibition of CGRPR, TRPV1, PLC, and PKC; cell viability and apoptosis assays in A549 cells under hyperoxia Molecular medicine reports Medium 38695251

Source papers

Stage 0 corpus · 47 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1999 The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells. FEBS letters 114 10217420
2000 CGRP and adrenomedullin binding correlates with transcript levels for calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) in rat tissues. British journal of pharmacology 112 10781016
2004 Effects of adrenomedullin on endothelial cells in the multistep process of angiogenesis: involvement of CRLR/RAMP2 and CRLR/RAMP3 receptors. International journal of cancer 111 14712479
2003 Transcriptional regulation of the CRLR gene in human microvascular endothelial cells by hypoxia. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 66 12824306
2002 Comparison of the expression of calcitonin receptor-like receptor (CRLR) and receptor activity modifying proteins (RAMPs) with CGRP and adrenomedullin binding in cell lines. British journal of pharmacology 64 12086988
2021 Adrenomedullin-CALCRL axis controls relapse-initiating drug tolerant acute myeloid leukemia cells. Nature communications 53 33462236
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
2002 Respective roles of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP) in cell surface expression of CRLR/RAMP heterodimeric receptors. The Journal of biological chemistry 49 11854283
2020 Molecular Insight into Recognition of the CGRPR Complex by Migraine Prevention Therapy Aimovig (Erenumab). Cell reports 44 32049005
2000 Dexamethasone increases RAMP1 and CRLR mRNA expressions in human vascular smooth muscle cells. Biochemical and biophysical research communications 40 10772950
2019 The neuropeptide receptor calcitonin receptor-like (CALCRL) is a potential therapeutic target in acute myeloid leukemia. Leukemia 38 31182782
2007 Assembly and signaling of CRLR and RAMP1 complexes assessed by BRET. Biochemistry 38 17503773
2004 RAMPs and CRLR expressions in osteoblastic cells after dexamethasone treatment. Biochemical and biophysical research communications 33 15358098
2001 Immunohistochemical detection of calcitonin gene-related peptide receptor (CGRPR)-1 in the endothelium of human coronary artery and bronchial blood vessels. Neuropeptides 30 11346311
2001 Adrenomedullin signalling in cardiomyocytes is dependent upon CRLR and RAMP2 expression. Peptides 28 11754972
2001 Glycosylation of human CRLR at Asn123 is required for ligand binding and signaling. Biochimica et biophysica acta 26 11389975
2019 CGRP Signaling via CALCRL Increases Chemotherapy Resistance and Stem Cell Properties in Acute Myeloid Leukemia. International journal of molecular sciences 25 31756985
2003 Evidence for the existence of a new receptor for CGRP, which is not CRLR. Peptides 24 12576086
2003 N-Glycosylation and conserved cysteine residues in RAMP3 play a critical role for the functional expression of CRLR/RAMP3 adrenomedullin receptor. Biochemistry 23 12939163
2001 Receptor activity modifying proteins interaction with human and porcine calcitonin receptor-like receptor (CRLR) in HEK-293 cells. Molecular and cellular biochemistry 23 11693189
2019 Mutant RAMP2 causes primary open-angle glaucoma via the CRLR-cAMP axis. Genetics in medicine : official journal of the American College of Medical Genetics 19 31000793
2017 The Application of CGRP(r) Monoclonal Antibodies in Migraine Spectrum: Needs and Priorities. BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 18 29124668
2021 Calcitonin receptor-like (CALCRL) is a marker of stemness and an independent predictor of outcome in pediatric AML. Blood advances 16 34559198
2019 CGRP-CRLR/RAMP1 signal is important for stress-induced hematopoiesis. Scientific reports 15 30674976
2009 Investigation of the association between CALCRL polymorphisms and primary angle closure glaucoma. Molecular vision 15 19898635
2005 Post-transcriptional regulation of CRLR expression during hypoxia. Biochemical and biophysical research communications 15 15567147
2004 The immunohistochemical expression of calcitonin receptor-like receptor (CRLR) in human gliomas. Journal of clinical pathology 15 14747444
2021 To Probe the Binding Interactions between Two FDA Approved Migraine Drugs (Ubrogepant and Rimegepant) and Calcitonin-Gene Related Peptide Receptor (CGRPR) Using Molecular Dynamics Simulations. ACS chemical neuroscience 14 34184869
2016 Cardiovascular effects of exogenous adrenomedullin and CGRP in Ramp and Calcrl deficient mice. Peptides 14 27940069
2006 Two novel cell specific receptor proteins, CRLR and CD 117 in human glial tumors. Clinical neuropathology 10 16719406
2001 Phenotypic changes of adrenomedullin receptor components, RAMP2, and CRLR mRNA expression in cultured rat vascular smooth muscle cells. Biochemical and biophysical research communications 9 11676473
2023 Expression of the Calcitonin Receptor-like Receptor (CALCRL) in Normal and Neoplastic Tissues. International journal of molecular sciences 7 36835377
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
1999 Equipotent in vitro actions of alpha- and beta-CGRP on guinea pig basilar artery are likely to be mediated via CRLR derived CGRP receptors. Regulatory peptides 7 10651059
2024 CALCRL knockdown suppresses cancer stemness and chemoresistance in acute myeloid leukemia with FLT3-ITD and DNM3TA-R882 double mutations. Drug development research 4 38349260
2024 Coronary Artery Disease Risk Variant Dampens the Expression of CALCRL by Reducing HSF Binding to Shear Stress Responsive Enhancer in Endothelial Cells In Vitro. Arteriosclerosis, thrombosis, and vascular biology 3 38602103
2023 CALCRL induces resistance to daunorubicin in acute myeloid leukemia cells through upregulation of XRCC5/TYK2/JAK1 pathway. Anti-cancer drugs 3 37948318
2022 Virtual drug repurposing study for the CGRPR identifies pentagastrin and leuprorelin as putative candidates. Journal of molecular graphics & modelling 3 35803082
2020 Calcitonin gene-related peptide receptor Calcrl is enriched in hair follicles stem cells and differentially expressed in interfollicular epidermis in murine skin. Neuroreport 3 32576770
2021 Short tandem repeat near hypoxia response element (HRE) instead of HRE genetic variants in promoter calcitonin receptor-like receptor (CRLR) gene as risk factor in severe preeclampsia: a preliminary study. BMC research notes 2 33413630
2025 miR-101-3p overexpression suppresses NSCLC progression through Immune-Related gene CALCRL regulation and lncRNA NEAT1 axis. Molecular biology reports 1 40974392
2024 Calcitonin gene‑related peptide alleviates hyperoxia‑induced human alveolar cell injury via the CGRPR/TRPV1/Ca2+ axis. Molecular medicine reports 1 38695251
2024 Spinal RAMP1-mediated neuropathic pain sensitisation in the aged mice through the modulation of CGRP-CRLR pain signalling. Heliyon 1 39224276
2026 Identification of the key immune and inflammatory related gene CALCRL as diagnostic biomarker in differentiating uterine leiomyosarcoma from leiomyoma. Frontiers in cell and developmental biology 0 42039143
2025 [Migraine patients treated with CGRP(R) antibodies : Are they different from patients treated with nonspecific oral prophylaxis? Analysis from the DMKG headache registry]. Schmerz (Berlin, Germany) 0 40932510
2025 Spinal Calcrl+ neurons amplify mechanical itch signaling via synaptic plasticity in chronic itch model. PloS one 0 41248150
2025 Hyperglycemia Increased The Expression of CALCRL G Protein-Coupled Receptor in Monocytes from Diabetic Patients. Cell journal 0 41420470

Missed literature

Know a paper Affinage missed for CALCRL? Flag it for the maintainers and the community.

No submissions yet.