Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels
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Authors
Lee, Moon Y.
Park, Chanjae
Ha, Se E.
Park, Paul J.
Berent, Robyn M.
Jorgensen, Brian G.
Corrigan, Robert D.
Grainger, Nathan
Blair, Peter J.
Slivano, Orazio J.
Issue Date
2017
Type
Article
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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 Cacnalc 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.
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Citation
Lee, M. Y., Park, C., Ha, S. E., Park, P. J., Berent, R. M., Jorgensen, B. G., … Ro, S. (2017). Serum response factor regulates smooth muscle contractility via myotonic dystrophy protein kinases and L-type calcium channels. PLOS ONE, 12(2), e0171262. doi:10.1371/journal.pone.0171262
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Creative Commons Attribution 4.0 International
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PubMed ID
ISSN
1932-6203