Desmin interacts with STIM1 and coordinates Ca2+ signaling in skeletal muscle.

Journal Article (Journal Article)

Stromal interaction molecule 1 (STIM1), the sarcoplasmic reticulum (SR) transmembrane protein, activates store-operated Ca2+ entry (SOCE) in skeletal muscle and, thereby, coordinates Ca2+ homeostasis, Ca2+-dependent gene expression, and contractility. STIM1 occupies space in the junctional SR membrane of the triads and the longitudinal SR at the Z-line. How STIM1 is organized and is retained in these specific subdomains of the SR is unclear. Here, we identified desmin, the major type III intermediate filament protein in muscle, as a binding partner for STIM1 based on a yeast 2-hybrid screen. Validation of the desmin-STIM1 interaction by immunoprecipitation and immunolocalization confirmed that the CC1-SOAR domains of STIM1 interact with desmin to enhance STIM1 oligomerization yet limit SOCE. Based on our studies of desmin-KO mice, we developed a model wherein desmin connected STIM1 at the Z-line in order to regulate the efficiency of Ca2+ refilling of the SR. Taken together, these studies showed that desmin-STIM1 assembles a cytoskeletal-SR connection that is important for Ca2+ signaling in skeletal muscle.

Full Text

Duke Authors

Cited Authors

  • Zhang, H; Bryson, VG; Wang, C; Li, T; Kerr, JP; Wilson, R; Muoio, DM; Bloch, RJ; Ward, C; Rosenberg, PB

Published Date

  • September 8, 2021

Published In

Volume / Issue

  • 6 / 17

PubMed ID

  • 34494555

Pubmed Central ID

  • PMC8492340

Electronic International Standard Serial Number (EISSN)

  • 2379-3708

Digital Object Identifier (DOI)

  • 10.1172/jci.insight.143472


  • eng

Conference Location

  • United States