Desmin interacts with STIM1 and coordinates Ca2+ signaling in skeletal muscle
Hengtao Zhang, Victoria Graham Bryson, Chaojian Wang, TianYu Li, Jaclyn P. Kerr, Rebecca Wilson, Deborah M. Muoio, Robert J. Bloch, Christopher Ward, Paul B. Rosenberg
Hengtao Zhang, Victoria Graham Bryson, Chaojian Wang, TianYu Li, Jaclyn P. Kerr, Rebecca Wilson, Deborah M. Muoio, Robert J. Bloch, Christopher Ward, Paul B. Rosenberg
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Research Article Muscle biology

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

Abstract

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.

Authors

Hengtao Zhang, Victoria Graham Bryson, Chaojian Wang, TianYu Li, Jaclyn P. Kerr, Rebecca Wilson, Deborah M. Muoio, Robert J. Bloch, Christopher Ward, Paul B. Rosenberg

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Figure 7

Ca2+ handling of SR Ca2+ store in the permeabilized WT and desmin KO FDB fibers and electrically evoked Ca2+ transients in desmin KO muscle fibers.

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Ca2+ handling of SR Ca2+ store in the permeabilized WT and desmin KO FDB...
(A) Flou-3 loaded FDB fibers from WT and DES-KO mice were electrically stimulated at 50 Hz for 2 seconds and Ca2+ transients were determined using a fast image acquisition system. The inset in A shows the enlarged view of decay of Ca2+ transients after termination of electrical stimulation. The decay time was determined for fibers after stimulation was terminated by fitting with 2 order exponentials. The decay time for DES-KO fibers (n = 60, P < 0.0001) was significantly slower than that in WT fibers (n = 45). (B and C) The summarized data for decay times and peak amplitude of Ca2+ transients from WT control and DES-KO mouse skeletal fibers after 2-second stimulation pulse. The reduction observed in DES-KO did not reach statistical significance. (D) Representative trace of Fluo-5N fluorescence after Ca2+ release from SR store by 30 mM caffeine and Ca2+ uptake by SR to specific [Ca2+]cyto as indicated in the saponin-permeabilized WT and DES-KO mouse FDB muscle fibers. (E) Fitting curves and R2 of Ca2+ uptake by SR after Ca2+ release in the WT (black circle, n = 81) and DES-KO (red filled circles, n = 57) FDB muscle fibers. A significant increase (P < 0.0001) was noted in the WT FDB fiber at 400 nM and 1 μM [Ca2+]cyto than in the DES-KO fibers.