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

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

Research output: Contribution to journalArticle

5 Scopus citations

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.

Original languageEnglish (US)
Article numbere0171262
JournalPloS one
Volume12
Issue number2
DOIs
StatePublished - Feb 1 2017

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Lee, M. Y., Park, C., Ha, S. E., Park, P. J., Berent, R. M., Jorgensen, B. G., Corrigan, R. D., Grainger, N., Blair, P. J., Slivano, O. J., Miano, J. M., Ward, S. M., Smith, T. K., Sanders, K. M., & 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]. https://doi.org/10.1371/journal.pone.0171262