Hdl Handle:
http://hdl.handle.net/10675.2/551
Title:
Impaired membrane resealing and autoimmune myositis in synaptotagmin VIIâ deficient mice
Authors:
Chakrabarti, Sabyasachi; Kobayashi, Koichi S.; Flavell, Richard A. ( 0000-0003-4461-0778 ) ; Marks, Carolyn B.; Miyake, Katsuya; Liston, David R.; Fowler, Kimberly T.; Gorelick, Fred S.; Andrews, Norma W.
Abstract:
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):543-549
Issue Date:
18-Aug-2003
URI:
http://hdl.handle.net/10675.2/551
DOI:
10.1083/jcb.200305131
PubMed ID:
12925704
PubMed Central ID:
PMC2173791
Type:
Article
ISSN:
1540-8140
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorChakrabarti, Sabyasachien_US
dc.contributor.authorKobayashi, Koichi S.en_US
dc.contributor.authorFlavell, Richard A.en_US
dc.contributor.authorMarks, Carolyn B.en_US
dc.contributor.authorMiyake, Katsuyaen_US
dc.contributor.authorListon, David R.en_US
dc.contributor.authorFowler, Kimberly T.en_US
dc.contributor.authorGorelick, Fred S.en_US
dc.contributor.authorAndrews, Norma W.en_US
dc.date.accessioned2012-10-26T16:26:37Z-
dc.date.available2012-10-26T16:26:37Z-
dc.date.issued2003-08-18en_US
dc.identifier.citationJ Cell Biol. 2003 Aug 18; 162(4):543-549en_US
dc.identifier.issn1540-8140en_US
dc.identifier.pmid12925704en_US
dc.identifier.doi10.1083/jcb.200305131en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/551-
dc.description.abstractMembers 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.en_US
dc.rightsCopyright © 2003, The Rockefeller University Pressen_US
dc.subjectReporten_US
dc.titleImpaired membrane resealing and autoimmune myositis in synaptotagmin VIIâ deficient miceen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2173791en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-

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