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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

31 CLR and RAMP1 were detected in perivascular nerves and arterial

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

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

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

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

36 xpressed glial fibrillary acidic protein and RAMP1.

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

38 cies selectivity was directed exclusively by RAMP1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

64 inity of small molecule antagonists for CRLR/RAMP1.

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

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

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

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

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

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

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

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

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

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

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

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

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

78 4 days) of HAECs with CRLR or RAMP2, but not RAMP1 or RAMP3, siRNAs abolished protection by IMD (1 nm

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

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

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

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

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

84 Knockdown of RAMP1 by shRNA decreased prostate cancer cell proliferat

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

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

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

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

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

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

91 The N-terminus of RAMP1 comprises three helices.

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

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

94 e ganglia express the CGRP1 receptor protein RAMP1.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

111 transient transfection into COS-7 cells with RAMP1.

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

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

114 ith similar affinities when coexpressed with RAMP1.

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

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

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

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