STIM1 signalling controls store-operated calcium entry required for development and contractile function in skeletal muscle.
It is now well established that stromal interaction molecule 1 (STIM1) is the calcium sensor of endoplasmic reticulum stores required to activate store-operated calcium entry (SOC) channels at the surface of non-excitable cells. However, little is known about STIM1 in excitable cells, such as striated muscle, where the complement of calcium regulatory molecules is rather disparate from that of non-excitable cells. Here, we show that STIM1 is expressed in both myotubes and adult skeletal muscle. Myotubes lacking functional STIM1 fail to show SOC and fatigue rapidly. Moreover, mice lacking functional STIM1 die perinatally from a skeletal myopathy. In addition, STIM1 haploinsufficiency confers a contractile defect only under conditions where rapid refilling of stores would be needed. These findings provide insight into the role of STIM1 in skeletal muscle and suggest that STIM1 has a universal role as an ER/SR calcium sensor in both excitable and non-excitable cells.
Stiber
Jonathan
J
Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Hawkins
April
A
Zhang
Zhu-Shan
ZS
Wang
Sunny
S
Burch
Jarrett
J
Graham
Victoria
V
Ward
Cary C
CC
Seth
Malini
M
Finch
Elizabeth
E
Malouf
Nadia
N
Williams
R Sanders
RS
Eu
Jerry P
JP
Rosenberg
Paul
P
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D020013:Calcium Signaling; D002460:Cell Line; D020868:Gene Silencing; D008562:Membrane Glycoproteins / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008954:Models, Biological; D008957:Models, Genetic; D009119:Muscle Contraction; D009132:Muscles / Q000378:metabolism; D018408:Patch-Clamp Techniques; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D015398:Signal Transduction; D000071737:Stromal Interaction Molecule 1
D015220:Calcium Channels; D008562:Membrane Glycoproteins; C100757:Stim1 protein, mouse; D000071737:Stromal Interaction Molecule 1; D002118:Calcium