Nature Cell Biology4, 379 - 383 (2002)
Published online: 22 April 2002; | doi:10.1038/ncb788
Dysfunction of store-operated calcium channel in muscle cells lacking mg29
Zui Pan1, Dongmei Yang2, 3, Ramakrishnan Y. Nagaraj1, Thomas A. Nosek4, Miyuki Nishi5, Hiroshi Takeshima5, Heping Cheng2
& Jianjie Ma1
1
Department of Physiology and Biophysics, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 675 Hoes Lane, Piscataway NJ 08854, USA
2
Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, 5600 Nathan Shock Drive, Baltimore MD 21224, USA
3
National Laboratory of Biomembrane and Membrane Biotechnology, College of Life Sciences, Peking University, Beijing 100871, China
4
Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, OH 44106, USA
5
Department of Biochemistry, Tohoku University Graduate School of Medicine and CREST, Japan Science and Technology Corporation, Sendai 980-8575, Japan
Correspondence should be addressed to Jianjie Ma maj2@umdnj.edu
The store-operated calcium channel (SOC) located in the plasma membrane (PM) mediates capacitative entry of extracellular calcium after depletion of intracellular calcium stores in the endoplasmic or sarcoplasmic reticulum (ER/SR)1,
2. An intimate interaction between the PM and the ER/SR is essential for the operation of this calcium signalling pathway3,
4,
5. Mitsugumin 29 (MG29) is a synaptophysin-family-related protein located in the junction between the PM and SR of skeletal muscle6,
7. Here, we identify SOC in skeletal muscle and characterise its regulation by MG29 and the ryanodine receptor (RyR) located in the SR. Targeted deletion of mg29 alters the junctional membrane structure, causes severe dysfunction of SOC and SR calcium homeostasis and increases the susceptibility of muscle to fatigue stimulation8. Severe dysfunction of SOC is also identified in muscle cells lacking both type 1 and type 3 RyRs, indicating that SOC activation requires an intact interaction between the PM and the SR, and is linked to conformational changes of RyRs. Whereas defective SOC seems to be inconsequential to short-term excitation−contraction coupling, the slow cumulative calcium entry through SOC is crucial for long-term calcium homeostasis, such that reduced SOC activity exaggerates muscle fatigue under conditions of intensive exercise.
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