ライフサイエンスコーパス: RAMP1

1 RAMP1 is a coreceptor for certain G-protein-coupled rece

2 RAMP1 mRNA expression was also detected in the posterior

3 RAMP1 presents the receptor at the cell surface as a mat

4 RAMP1 was also localized to enteric and DRG neurons and

5 RAMP1 was degraded approximately 4-fold more rapidly tha

6 RAMP1/2 alter CLR selectivity for CGRP/AM in part by RAM

7 s via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CALCRL

8 s via receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor (CALCRL

9 y the receptor activity-modifying protein 1 (RAMP1) as a direct NKX3.1 target gene through analysis o

10 with receptor activity-modifying protein 1 (RAMP1) at the cell surface to form heterodimeric recepto

11 ) and receptor activity modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene related p

12 d the receptor activity-modifying protein 1 (RAMP1) comprise a receptor for calcitonin gene-related p

13 Receptor activity modifying protein 1 (RAMP1) is an integral component of several receptors inc

14 rough receptor activity modifying protein 1 (RAMP1) on meningeal macrophages to polarize their transc

15 ) and receptor activity-modifying protein 1 (RAMP1), and the distribution of PACAP and glutamate in r

16 CLR), receptor activity-modifying protein 1 (RAMP1), beta-arrestin2, and ECE-1 to early endosomes, wh

17 gene, receptor activity-modifying protein 1 (RAMP1), can be a modifier of photophobia and, by extensi

18 on of Receptor activity modifying protein 1 (RAMP1), Nuclear receptor 1 (NR4A1) and other Cyclin gene

19 ) and receptor activity-modifying protein 1 (RAMP1), respectively.

20 ptor, receptor activity modifying protein 1 (RAMP1).

21 ) and receptor activity-modifying protein 1 (RAMP1).

22 s (EC receptor activity modifying protein 1 [RAMP1] knockout mice).

23 eceptor activity-modifying protein (RAMP)-1, RAMP1 (AMY(1)R), human RAMP2 (AMY(2)R), or human RAMP3 (

24 n addition, our study showed that a CGRP8-37-RAMP1 chimera, but not RAMP1, functions as an antagonist

25 eptors comprising the class B GPCR CLR and a RAMP1, -2, or -3 modulatory subunit.

26 orted increased endometrial cell growth in a RAMP1-dependent manner.

27 Moreover, a RAMP1 mutant lacking the only intracellular lysine (RAMP

28 Here, we show that the fusion of a RAMP1 co-receptor with the calcitonin gene-related pepti

29 a G protein-coupled receptor, paired with a RAMP1, RAMP2, or RAMP3 accessory subunit, respectively,

30 derived stem cells, CGRP induces CALCRL- and RAMP1-dependent activation of cAMP-responsive element bi

31 Some neurons expressing CLR and RAMP1 co-localized with glutamate.

32 ptor comprising a heterodimer of the CLR and RAMP1 ECDs.

33 ibodies specifically interacted with CLR and RAMP1 in HEK cells coexpressing rat CLR and RAMP1, deter

34 escence revealed expression of CGRP, CLR and RAMP1 in trigeminal cells.

35 Thus, CLR and RAMP1 may mediate the effects of CGRP and intermedin in

36 CLR and RAMP1 mRNA and protein expression were detected in the p

37 After sustained stimulation, CLR and RAMP1 traffic from endosomes to lysosomes by ubiquitin-i

38 ter transient stimulation with CGRP, CLR and RAMP1 traffic from endosomes to the plasma membrane, whi

39 nal nucleus; protein coexpression of CLR and RAMP1 was observed in these areas via immunofluorescence

40 Recycling CLR and RAMP1 were detected in endosomes containing Rab4a and Ra

41 CLR and RAMP1 were detected in perivascular nerves and arterial

42 RAMP1 in HEK cells coexpressing rat CLR and RAMP1, determined by Western blotting and immunofluoresc

43 se proteins, we raised antibodies to CLR and RAMP1.

44 s is known about the localization of CLR and RAMP1.

45 he surface of these cells and CGRP, CLR, and RAMP1 internalized into the same endosomes.

46 xpressed glial fibrillary acidic protein and RAMP1.

47 d MAs, sensory nerve density was reduced and RAMP1 (CGRP receptor component) associated with nuclear

48 cies selectivity was directed exclusively by RAMP1.

49 alter CLR selectivity for CGRP/AM in part by RAMP1 Trp-84 or RAMP2 Glu-101 contacting the distinct CG

50 ar affinity, the anchored CGRP-RAMP1 and CAL-RAMP1 ligands confine their activities to individual cel

51 embrane-anchored ligands (CGRP-RAMP1 and CAL-RAMP1).

52 The CAL-RAMP1 selectively activates the calcitonin receptor (CR)

53 Components of the receptor for CGRP (RAMP1 and CLR) were expressed in a very small subset of

54 n of the receptor for the neuropeptide CGRP, RAMP1, in CD8(+) T lymphocytes induced by skin commensal

55 sed on molecular affinity, the anchored CGRP-RAMP1 and CAL-RAMP1 ligands confine their activities to

56 dministration-approved drugs that block CGRP-RAMP1 signaling reduced mechanical hyperalgesia, spontan

57 uggesting that the activation of CLR by CGRP-RAMP1 shares similar molecular mechanisms with the CGRP-

58 t RAMP1, functions as an antagonist for CGRP-RAMP1-mediated signaling, suggesting that the activation

59 Therefore, bacteria hijack CGRP-RAMP1 signalling in meningeal macrophages to facilitate

60 to bona fide membrane-anchored ligands (CGRP-RAMP1 and CAL-RAMP1).

61 The neuroimmune CGRP-RAMP1 signaling axis functions in commensal-specific T c

62 As such, modulation of neuroimmune CGRP-RAMP1 signaling in commensal-specific T cells shapes the

63 calcitonin receptor (CR), whereas, the CGRP-RAMP1 activates both the calcitonin receptor-like recept

64 tive immunity to the microbiota via the CGRP-RAMP1 axis underscores the various layers of regulation

65 mechanisms of nonhormonal and nonopioid CGRP/RAMP1 blockade in a mouse model of endometriosis, sugges

66 approximately 4-fold more rapidly than CLR (RAMP1, 45% degradation, 5 h; CLR, 54% degradation, 16 h)

67 CLR/RAMP1 activation in human and mouse Schwann cells genera

68 CLR/RAMP1 forms a CGRP receptor, CLR/RAMP2 forms an adrenome

69 r/receptor activity modifying protein-1, CLR/RAMP1) implicates peripherally-released CGRP in migraine

70 release cargo in acidified endosomes, a CLR/RAMP1 antagonist provides superior inhibition of CGRP si

71 ained stimulation (10(-7) M CGRP, >2 h), CLR/RAMP1 trafficked to lysosomes.

72 timulation (10(-7) M CGRP, 1 h), induced CLR/RAMP1 recycling with similar kinetics (2-6 h), demonstra

73 beta-arrestin2 in endosomes and inhibits CLR/RAMP1 recycling and resensitization, whereas ECE-1 overe

74 Recycling of CLR/RAMP1 correlated with resensitization of CGRP-induced in

75 sms with the CGRP-mediated activation of CLR/RAMP1 receptor complexes.

76 Although CGRP induces endocytosis of CLR/RAMP1, little is known about post-endocytic sorting of t

77 kedly affected post-endocytic sorting of CLR/RAMP1.

78 CGRP degradation promotes CLR/RAMP1 recycling and beta-arrestin2 redistribution to the

79 ouse cutaneous trigeminal fibers targets CLR/RAMP1 on surrounding Schwann cells to evoke periorbital

80 onists display a higher affinity for the CLR/RAMP1 complex than for CTR/RAMP1 provided an opportunity

81 ECE-1 inhibition or knockdown traps CLR/RAMP1 and beta-arrestin2 in endosomes and inhibits CLR/R

82 crystal structures of CGRP analog-bound CLR:RAMP1 and AM-bound CLR:RAMP2 extracellular domain hetero

83 These data demonstrate that CNS RAMP1 plays a pivotal role in the regulation of energy h

84 IMD and CRLR, RAMP1, RAMP2 and RAMP3 were expressed in all cell types.

85 F) with the CRLR-RAMP3 complex, but not CRLR-RAMP1 or CRLR-RAMP2 complex, altered receptor traffickin

86 inity of small molecule antagonists for CRLR/RAMP1.

87 By generating recombinant human/rat CRLR/RAMP1 receptors, we demonstrated that co-expression of h

88 peptide selectivity of intact CTR, AMY1 (CTR.RAMP1), and AMY2 (CTR.RAMP2) receptors using purified CT

89 inity for the CLR/RAMP1 complex than for CTR/RAMP1 provided an opportunity to investigate the molecul

90 In addition, EC RAMP1 knockout mice had significantly reduced contact hy

91 , which raises the possibility that elevated RAMP1 might sensitize some individuals to CGRP actions i

92 Furthermore, RAMP1 mRNA and protein levels are significantly higher i

93 ity for the human receptor, human CRLR/human RAMP1, than for the rat receptor, rat CRLR/rat RAMP1.

94 assessed the effect of overexpressing human RAMP1 (hRAMP1) in the CNS on body energy balance.

95 Moreover, with rat/human RAMP1 chimeras and site-directed mutants, we have identi

96 d pathways that are significantly altered in RAMP1 knockdown cells, including the mitogen-activated p

97 llular signal-regulated kinase 1/2 levels in RAMP1 knockdown cells.

98 esent in the C terminus of RAMP3, but not in RAMP1 or RAMP2, leads to protein-protein interactions th

99 nts with melanoma revealed that intratumoral RAMP1-expressing CD8(+) T cells were more exhausted than

100 Accordingly, mutant RAMP1 W84A- and RAMP2 E101A-CTR ECD retained AC413/rAmy

101 nctional significance of modulating neuronal RAMP1, we assessed the effect of overexpressing human RA

102 e interaction of MRGPRX4 with RAMP2, but not RAMP1 or 3, causes attenuation of basal and agonist-depe

103 4 days) of HAECs with CRLR or RAMP2, but not RAMP1 or RAMP3, siRNAs abolished protection by IMD (1 nm

104 howed that a CGRP8-37-RAMP1 chimera, but not RAMP1, functions as an antagonist for CGRP-RAMP1-mediate

105 esidues 23-133 of CLR and residues 26-117 of RAMP1 were shown to be sufficient for formation of a sta

106 tified a single amino acid at position 74 of RAMP1 that modulates the affinity of small molecule anta

107 P1 deficiency or pharmacological blockade of RAMP1 enhanced immune responses and bacterial clearance

108 Co-expression of RAMP1 and CRLR reconstituted a CGRP receptor that was ab

109 residues spread throughout three helices of RAMP1, were mutated to alanine and coexpressed with CLR

110 Knockdown of RAMP1 by shRNA decreased prostate cancer cell proliferat

111 est that genetic or epigenetic modulation of RAMP1 levels may contribute to migraine susceptibility.

112 tive counterparts, whereas overexpression of RAMP1 correlated with a poorer clinical prognosis.

113 e tumorigenesis and support the potential of RAMP1 as a novel biomarker and possible therapeutic targ

114 so interact with the extracellular region of RAMP1 and could suggest the formation of a binding pocke

115 or reside within the extracellular region of RAMP1 and provide evidence that this receptor accessory

116 The current study investigated regions of RAMP1 important for CGRP or CLR interactions by alanine

117 data provide novel insights into the role of RAMP1 in promoting prostate tumorigenesis and support th

118 The N-terminus of RAMP1 comprises three helices.

119 indicating that other regions of CLR and/or RAMP1 are important for peptide agonist binding.

120 ctable mono- or polyubiquitination of CLR or RAMP1, determined by immunoprecipitation and Western blo

121 e ganglia express the CGRP1 receptor protein RAMP1.

122 single-pass transmembrane accessory protein (RAMP1) and a family B G-protein-coupled receptor (GPCR)

123 Receptor activity-modifying proteins (RAMP1-3) determine the selectivity of the class B G prot

124 three receptor activity-modifying proteins (RAMP1-3) that determine its peptide ligand selectivity.

125 ion of receptor activity-modifying proteins (RAMP1-3) with the G protein-coupled receptor (GPCR) calc

126 MP1, than for the rat receptor, rat CRLR/rat RAMP1.

127 Replacement of lysine 74 in rat RAMP1 with tryptophan (the homologous amino acid in the

128 ed that co-expression of human CRLR with rat RAMP1 produced rat receptor pharmacology, and vice versa

129 iceptors and antagonism of the CGRP receptor RAMP1 all reduced the exhaustion of tumour-infiltrating

130 er cell lines indicate that NKX3.1 represses RAMP1 expression.

131 By cell-selective RAMP1 gene deletion, we reveal that CGRP released from m

132 nteracted with TM7 did not display a similar RAMP1 dependence, suggesting an allosteric mechanism of

133 CGRP receptor proteins was similar in SMCs, RAMP1 associated with nuclear regions of endothelial cel

134 Macrophage-specific RAMP1 deficiency or pharmacological blockade of RAMP1 en

135 CTR extracellular domain (ECD) and tethered RAMP1- and RAMP2-CTR ECD fusion proteins and antagonist

136 These results demonstrate that RAMP1 is functionally rate limiting for CGRP receptor ac

137 We found that RAMP1 expression is specifically elevated in human prost

138 ting RAMP-GPCR interaction map suggests that RAMP1 and RAMP3 interact with the same set of GPCRs, whi

139 ntified multiple NKX3.1 binding sites in the RAMP1 locus in human prostate cancer cells and in the no

140 CGRP and AM prefer the RAMP1 and RAMP2/3 complexes, respectively, whereas AM2/I

141 eptide (CGRP), or calcitonin, transforms the RAMP1 from a co-receptor to bona fide membrane-anchored

142 D8(+) T cells were more exhausted than their RAMP1-negative counterparts, whereas overexpression of R

143 To establish whether RAMP1 is limiting in vivo as indicated from the culture

144 transient transfection into COS-7 cells with RAMP1.

145 Dimerization of CLR with RAMP1 provides specificity for CGRP versus related agoni

146 as disrupted when P321A was coexpressed with RAMP1, RAMP2, or RAMP3.

147 ith similar affinities when coexpressed with RAMP1.

148 l stimulation of CRLR when co-expressed with RAMP1 and RAMP2 or RAMP3, respectively, intermedin repre

149 d by NHERF-1 when CRLR was co-expressed with RAMP1 or RAMP2.

150 ceptor (CRLR), while a CRLR heterodimer with RAMP1 yields a calcitonin gene-related peptide receptor.

151 ciates specifically with RAMP3, but not with RAMP1 or RAMP2.