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Calcitonin gene‐related peptide induces the expression of acetylcholinesterase‐associated collagen ColQ in muscle: a distinction in driving two different promoters between fast‐ and slow‐twitch muscle fibers
Author(s) -
Choi Roy C. Y.,
Ting Annie K. L.,
Lau Faye T. C.,
Xie Heidi Q.,
Leung K. Wing,
Chen Vicky P.,
Siow Nina L.,
Tsim Karl W. K.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2007.04630.x
Subject(s) - calcitonin gene related peptide , acetylcholinesterase , neuromuscular junction , biology , gene expression , microbiology and biotechnology , chemistry , endocrinology , medicine , gene , receptor , neuropeptide , biochemistry , neuroscience , enzyme
The presence of a collagenous protein (ColQ) characterizes the collagen‐tailed forms of acetylcholinesterase at vertebrate neuromuscular junctions (nmjs). Two ColQ transcripts as ColQ‐1 and ColQ‐1a, driven by two promoters: pColQ‐1 and pColQ‐1a, were found in mammalian slow‐ and fast‐twitch muscles, respectively, which have distinct expression pattern in different muscle fibers. In this study, we show the differential expression of CoQ in different muscles is triggered by calcitonin gene‐related peptide (CGRP), a known motor neuron‐derived factor. Application of CGRP, or dibutyryl‐cAMP (Bt 2 ‐cAMP), in cultured myotubes induced the expression of ColQ‐1a transcript and promoter activity; however, the expression of ColQ‐1 transcript did not respond to CGRP or Bt 2 ‐cAMP. The CGRP‐induced gene activation was blocked by an adenylyl cyclase inhibitor or a dominant negative mutant of cAMP‐responsive element (CRE) binding protein (CREB). Two CRE sites were mapped within the ColQ‐1a promoter, and mutations of the CRE sites abolished the response of CGRP or Bt 2 ‐cAMP. In parallel, CGRP receptor complex was dominantly expressed at the nmjs of fast muscle but not of slow muscle. These results suggested that the expression of ColQ‐1a at the nmjs of fast‐twitch muscle was governed by a CGRP‐mediated cAMP signaling mechanism.