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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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ADP-Ribosylation Factor 6
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ADP-Ribosylation Factors / metabolism*
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Animals
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Caenorhabditis elegans / genetics
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Caenorhabditis elegans / metabolism*
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Caenorhabditis elegans Proteins / genetics
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Caenorhabditis elegans Proteins / metabolism*
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Calcium-Binding Proteins / metabolism*
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Cloning, Molecular
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Endocytosis / physiology*
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Green Fluorescent Proteins
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Luminescent Proteins
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Microscopy, Fluorescence
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Mutation
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Phosphatidylinositols / metabolism*
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Phosphoproteins / metabolism*
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Phosphoric Monoester Hydrolases
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Protein Binding
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Protein Structure, Tertiary
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Protein Transport / physiology
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Protein Tyrosine Phosphatases / genetics
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Protein Tyrosine Phosphatases / metabolism*
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Protein Tyrosine Phosphatases, Non-Receptor
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RNA, Small Interfering
Substances
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ADP-Ribosylation Factor 6
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Caenorhabditis elegans Proteins
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Calcium-Binding Proteins
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Luminescent Proteins
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Phosphatidylinositols
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Phosphoproteins
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RNA, Small Interfering
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phosphoinositide 3-phosphate
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Green Fluorescent Proteins
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MTM-6 protein, C elegans
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Phosphoric Monoester Hydrolases
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Protein Tyrosine Phosphatases
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Protein Tyrosine Phosphatases, Non-Receptor
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SBF2 protein, human
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mtm-9 protein, C elegans
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ADP-Ribosylation Factors
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ARF6 protein, human