Impaired membrane resealing and autoimmune myositis in synaptotagmin VIIâ deficient mice
Authors
Chakrabarti, SabyasachiKobayashi, Koichi S.
Flavell, Richard A.
Marks, Carolyn B.
Miyake, Katsuya
Liston, David R.
Fowler, Kimberly T.
Gorelick, Fred S.
Andrews, Norma W.
Issue Date
2003-08-18
Metadata
Show full item recordAbstract
Members of the synaptotagmin family have been proposed to function as Ca2+ sensors in membrane fusion. Syt VII is a ubiquitously expressed synaptotagmin previously implicated in plasma membrane repair and Trypanosoma cruzi invasion, events which are mediated by the Ca2+-regulated exocytosis of lysosomes. Here, we show that embryonic fibroblasts from Syt VII-deficient mice are less susceptible to trypanosome invasion, and defective in lysosomal exocytosis and resealing after wounding. Examination of mutant mouse tissues revealed extensive fibrosis in the skin and skeletal muscle. Inflammatory myopathy, with muscle fiber invasion by leukocytes and endomysial collagen deposition, was associated with elevated creatine kinase release and progressive muscle weakness. Interestingly, similar to what is observed in human polymyositis/dermatomyositis, the mice developed a strong antinuclear antibody response, characteristic of autoimmune disorders. Thus, defective plasma membrane repair in tissues under mechanical stress may favor the development of inflammatory autoimmune disease.Citation
J Cell Biol. 2003 Aug 18; 162(4):543-549ae974a485f413a2113503eed53cd6c53
10.1083/jcb.200305131
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