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PMID: 14565969 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Disease-related myotubularins function in endocytic traffic in Caenorhabditis elegans.

Molecular biology of the cell ·Vol. 15 ·No. 1 ·2004-01-00 ·Pages 189-96

Dang H, Li Z, Skolnik EY, Fares H

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.

MeSH Terms
ADP-Ribosylation Factor 6 ADP-Ribosylation Factors/metabolism Animals Caenorhabditis elegans/genetics,metabolism Caenorhabditis elegans Proteins/genetics,metabolism Calcium-Binding Proteins/metabolism Cloning, Molecular Endocytosis/physiology Green Fluorescent Proteins Luminescent Proteins Microscopy, Fluorescence Mutation Phosphatidylinositols/metabolism Phosphoproteins/metabolism Phosphoric Monoester Hydrolases Protein Binding Protein Structure, Tertiary Protein Transport/physiology Protein Tyrosine Phosphatases/genetics,metabolism Protein Tyrosine Phosphatases, Non-Receptor RNA, Small Interfering
Chemicals
ADP-Ribosylation Factor 6 Caenorhabditis elegans Proteins Calcium-Binding Proteins Luminescent Proteins Phosphatidylinositols Phosphoproteins RNA, Small Interfering phosphoinositide 3-phosphate Green Fluorescent Proteins MTM-6 protein, C elegans Phosphoric Monoester Hydrolases Protein Tyrosine Phosphatases Protein Tyrosine Phosphatases, Non-Receptor SBF2 protein, human mtm-9 protein, C elegans ADP-Ribosylation Factors ARF6 protein, human
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dang Hope
Department of Molecular and Cellular Biology, University of Arizona, Tucson, Arizona 85721, USA.
Li Zhai
Skolnik Edward Y
Fares Hanna
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1059-1524
DOI
10.1091/mbc.e03-08-0605
Published
2004-01-00
Epub
2003-00-17
Pages
189-96
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC307539
Subset
IM
External Links
PubMed source DOI: 10.1091/mbc.e03-08-0605 PMC Full Text View journal details
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