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  • Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels.

Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels.

PloS one (2017-02-06)
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
ABSTRACT

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 Ca2+ 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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Goat Anti-Rabbit IgG Antibody, (H+L) HRP conjugate, 1 mg/mL, Chemicon®
Sigma-Aldrich
Goat Anti-Guinea Pig IgG Antibody, HRP conjugate, Chemicon®, from goat