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Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice

Members of the synaptotagmin family have been proposed to function as Ca(2+) 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 Ca(2+)-regulated exocytosis of l...

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Autores principales: Chakrabarti, Sabyasachi, Kobayashi, Koichi S., Flavell, Richard A., Marks, Carolyn B., Miyake, Katsuya, Liston, David R., Fowler, Kimberly T., Gorelick, Fred S., Andrews, Norma W.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2003
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173791/
https://www.ncbi.nlm.nih.gov/pubmed/12925704
http://dx.doi.org/10.1083/jcb.200305131
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author Chakrabarti, Sabyasachi
Kobayashi, Koichi S.
Flavell, Richard A.
Marks, Carolyn B.
Miyake, Katsuya
Liston, David R.
Fowler, Kimberly T.
Gorelick, Fred S.
Andrews, Norma W.
author_facet Chakrabarti, Sabyasachi
Kobayashi, Koichi S.
Flavell, Richard A.
Marks, Carolyn B.
Miyake, Katsuya
Liston, David R.
Fowler, Kimberly T.
Gorelick, Fred S.
Andrews, Norma W.
author_sort Chakrabarti, Sabyasachi
collection PubMed
description Members of the synaptotagmin family have been proposed to function as Ca(2+) 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 Ca(2+)-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.
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spelling pubmed-21737912008-05-01 Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice Chakrabarti, Sabyasachi Kobayashi, Koichi S. Flavell, Richard A. Marks, Carolyn B. Miyake, Katsuya Liston, David R. Fowler, Kimberly T. Gorelick, Fred S. Andrews, Norma W. J Cell Biol Report Members of the synaptotagmin family have been proposed to function as Ca(2+) 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 Ca(2+)-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. The Rockefeller University Press 2003-08-18 /pmc/articles/PMC2173791/ /pubmed/12925704 http://dx.doi.org/10.1083/jcb.200305131 Text en Copyright © 2003, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Report
Chakrabarti, Sabyasachi
Kobayashi, Koichi S.
Flavell, Richard A.
Marks, Carolyn B.
Miyake, Katsuya
Liston, David R.
Fowler, Kimberly T.
Gorelick, Fred S.
Andrews, Norma W.
Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice
title Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice
title_full Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice
title_fullStr Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice
title_full_unstemmed Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice
title_short Impaired membrane resealing and autoimmune myositis in synaptotagmin VII–deficient mice
title_sort impaired membrane resealing and autoimmune myositis in synaptotagmin vii–deficient mice
topic Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2173791/
https://www.ncbi.nlm.nih.gov/pubmed/12925704
http://dx.doi.org/10.1083/jcb.200305131
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