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BMC Molecular Biology

, 6:7

First Online: 24 March 2005Received: 01 October 2004Accepted: 24 March 2005

Abstract

BackgroundReceptor activity modifying protein-1 RAMP-1 is a single transmembrane-domain protein required for the functional expression of calcitonin gene-related peptide CGRP receptors. To date, little is known about the molecular mechanisms that activate-inhibit RAMP-1 gene expression. Such mechanisms are likely to play a major role in modulating the responsiveness of tissues to CGRP.

ResultsTo initiate studies on the transcriptional regulation of the mouse RAMP-1 gene, RAMP-1 transcriptional initiation sites were mapped in a variety of tissues. Analysis of RAMP-1 expression in C2C12 myoblasts demonstrated that RAMP-1 mRNA is expressed at greatest levels in confluent myoblasts verses non-confluent and fused myoblasts. Transfection of confluent C2C12 myoblasts and NIH 3T3 cells with RAMP-1 promoter-luciferase deletion constructs revealed that 4.7 kb of RAMP-1 5- flanking region demonstrated optimal promoter activity while 343 bp of 5- flanking region was defined as a minimal RAMP-1 promoter. In non-RAMP-1 expressing HEK293 cells, constructs containing 4.7 kb to 782 bp of RAMP-1 5- flanking region were transcriptionally inactive. However, deletion of sequences -782 to -343 activated RAMP-1 promoter activity.

ConclusionThese findings suggest that tissue specificity of RAMP-1 gene expression is mediated by a negative acting transcription factor that represses RAMP-1 gene expression in non-RAMP-1 expressing tissues. This transcription factor is therefore likely to play an important role in modulating the responsiveness of tissues to CGRP.

AbbreviationsCGRPcalcitonin gene related peptide

CTRcalcitonin receptor

RAMPreceptor activity modifying protein

GPCRG protein coupled receptor

CLcalcitonin receptor like

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2199-6-7 contains supplementary material, which is available to authorized users.

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Autor: Marc D Pondel - Richard Mould

Fuente: https://link.springer.com/







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