Respective roles of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP) in cell surface expression of CRLR/RAMP heterodimeric receptors.


Autoria(s): Flahaut M.; Rossier B.C.; Firsov D.
Data(s)

2002

Resumo

Receptor activity modifying proteins RAMP1, RAMP2, and RAMP3 are responsible for defining affinity to ligands of the calcitonin receptor-like receptor (CRLR). It has also been proposed that receptor activity-modifying proteins (RAMP) are molecular chaperones required for CRLR transport to the cell surface. Here, we have studied the respective roles of CRLR and RAMP in transporting CRLR/RAMP heterodimers to the plasma membrane by using a highly specific binding assay that allows quantitative detection of cell surface-expressed CRLR or RAMP in the Xenopus oocytes expression system. We show that: (i) heterodimer assembly is not a prerequisite for efficient cell surface expression of CRLR, (ii) N-glycosylated RAMP2 and RAMP3 are expressed at the cell surface and their transport to the plasma membrane requires N-glycans, (iii) RAMP1 is not N-glycosylated and is transported to the plasma membrane only upon formation of heterodimers with CRLR, and (iv) introduction of N-glycosylation sites in the RAMP1 sequence (D58N/G60S, Y71N, and K103N/P105S) allows cell surface expression of these mutants at levels similar to that of wild-type RAMP1 co-expressed with CRLR. Our data argue against a chaperone function for RAMP and identify the role of N-glycosylation in targeting these molecules to the cell surface.

Identificador

http://serval.unil.ch/?id=serval:BIB_81C4D4DE57EB

isbn:0021-9258 (Print)

pmid:11854283

doi:10.1074/jbc.M112084200

isiid:000175203000050

Idioma(s)

en

Fonte

Journal of Biological Chemistry, vol. 277, no. 17, pp. 14731-14737

Palavras-Chave #Animals; Calcitonin Receptor-Like Protein; Cell Membrane/metabolism; DNA, Complementary; Dimerization; Glycosylation; Intracellular Signaling Peptides and Proteins; Membrane Proteins/genetics; Membrane Proteins/physiology; Mice; Mutagenesis, Site-Directed; Receptor Activity-Modifying Protein 1; Receptor Activity-Modifying Protein 2; Receptor Activity-Modifying Protein 3; Receptor Activity-Modifying Proteins; Receptors, Calcitonin/physiology; Xenopus
Tipo

info:eu-repo/semantics/article

article