Affiliation:
1. Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721
2. Departments of Pharmacology and Cell Biology, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016
Abstract
MTM1, MTMR2, and SBF2 belong to a family of proteins called the myotubularins. X-linked myotubular myopathy, a severe congenital disorder characterized by hypotonia and generalized muscle weakness in newborn males, is caused by mutations in MTM1 ( Laporte et al., 1996 ). Charcot-Marie-Tooth types 4B1 and 4B2 are severe demyelinating neuropathies caused by mutations in MTMR2 ( Bolino et al., 2000 ) and SBF2/MTMR13 ( Senderek et al., 2003 ), respectively. Although several myotubularins are known to regulate phosphoinositide-phosphate levels in cells, little is known about the actual cellular process that is defective in patients with these diseases. Mutations in worm MTM-6 and MTM-9, myotubularins belonging to two subgroups, disorganize phosphoinositide 3-phosphate localization and block endocytosis in the coelomocytes of Caenorhabditis elegans. We demonstrate that MTM-6 and MTM-9 function as part of a complex to regulate an endocytic pathway that involves the Arf6 GTPase, and we define protein domains required for MTM-6 activity.
Publisher
American Society for Cell Biology (ASCB)
Subject
Cell Biology,Molecular Biology
Cited by
84 articles.
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