Open AccessSerum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels
Author(s) -
Moon Young Lee,
Chanjae Park,
Se Eun Ha,
Paul J. Park,
Robyn M Berent,
Brian G. Jorgensen,
Robert D. Corrigan,
Nathan Grainger,
Peter J. Blair,
Orazio J. Slivano,
Joseph M. Miano,
Sean M. Ward,
Terence K. Smith,
Kenton M. Sanders,
Seungil Ro
Publication year - 2017
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0171262
Subject(s) - serum response factor , contractility , myotonic dystrophy , biology , medicine , endocrinology , microbiology and biotechnology , gene expression , gene , biochemistry , genetics
Serum response factor (SRF) transcriptionally regulates expression of contractile genes in smooth muscle cells (SMC). Lack or decrease of SRF is directly linked to a phenotypic change of SMC, leading to hypomotility of smooth muscle in the gastrointestinal (GI) tract. However, the molecular mechanism behind SRF-induced hypomotility in GI smooth muscle is largely unknown. We describe here how SRF plays a functional role in the regulation of the SMC contractility via myotonic dystrophy protein kinase (DMPK) and L-type calcium channel CACNA1C. GI SMC expressed Dmpk and Cacna1c genes into multiple alternative transcriptional isoforms. Deficiency of SRF in SMC of Srf knockout (KO) mice led to reduction of SRF-dependent DMPK, which down-regulated the expression of CACNA1C. Reduction of CACNA1C in KO SMC not only decreased intracellular Ca 2+ spikes but also disrupted their coupling between cells resulting in decreased contractility. The role of SRF in the regulation of SMC phenotype and function provides new insight into how SMC lose their contractility leading to hypomotility in pathophysiological conditions within the GI tract.