HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 14, 13817-13824, April 2, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/14/13817    most recent M312294200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Tsujita, K. Articles by Takenawa, T. Search for Related Content PubMed PubMed Citation Articles by Tsujita, K. Articles by Takenawa, T. Social Bookmarking                      What's this?

Myotubularin Regulates the Function of the Late Endosome through the GRAM Domain-Phosphatidylinositol 3,5-Bisphosphate Interaction^*

Kazuya Tsujita, Toshiki Itoh, Takeshi Ijuin, Akitsugu Yamamoto, Assia Shisheva¶, Jocelyn Laporte||, and Tadaomi Takenawa**

From the Department of Biochemistry, Institute of Medical Science, University of Tokyo and Japan Science and Technology Corporation, Japan Science and Technology Corporation (JST), 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan, the Department of Bio-Science, Nagahama institute of Bio-Science and Technology, Tamura-cho, Nagahama 526-0829, Japan, the ^¶Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201, and the ^||Equipe Genetique Humaine Institute de Genetique et de Biologie Moleculaire et Cellulaire 1, rue Laurent Fries B. P., 10142-67404 Illkirch, France

Myotubularin and related proteins constitute a large and highly conserved family possessing phosphoinositide 3-phosphatase activity, although not all members possess this activity. This family contains a conserved region called the GRAM domain that is found in a variety of proteins associated with membrane-coupled processes and signal transduction. Mutations of myotubularin are found in X-linked myotubular myopathy, a severe muscle disease. Mutations in the GRAM domain are responsible for this condition, suggesting crucial roles for this region. Here, we show that the GRAM domain of myotubularin binds to phosphoinositide with the highest affinity to phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P₂). In patients with myotubular myopathy, mutations in the myotubularin GRAM domain eliminate this binding, indicating that the PtdIns(3,5)P₂ binding ability of the GRAM (glucosyltransferases, Rablike GTPase activators and myotubularin) domain is crucial for the functions of myotubularin in vivo. Stimulation of epidermal growth factor recruits myotubularin to the late endosomal compartment in a manner dependent on the phosphoinositide binding. Overexpression of myotubularin inhibits epidermal growth factor receptor trafficking from late endosome to lysosome and induces the large endosomal vacuoles. Thus, our data suggest that myotubularin phosphatase physiologically functions in late endosomal trafficking and vacuolar morphology through interaction with PtdIns(3,5)P₂.

Received for publication, November 10, 2003

^* This work was supported by National Institute of Health Grant DK-58058 (to A. S.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^** To whom correspondence should be addressed. Tel.: 81-3-5449-5510; Fax: 81-3-5449-5417; E-mail: takenawa{at}ims.u-tokyo.ac.jp.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Cao, J. M. Backer, J. Laporte, E. J. Bedrick, and A. Wandinger-Ness Sequential Actions of Myotubularin Lipid Phosphatases Regulate Endosomal PI(3)P and Growth Factor Receptor Trafficking Mol. Biol. Cell, August 1, 2008; 19(8): 3334 - 3346. [Abstract] [Full Text] [PDF]

				A. Buj-Bello, F. Fougerousse, Y. Schwab, N. Messaddeq, D. Spehner, C. R. Pierson, M. Durand, C. Kretz, O. Danos, A.-M. Douar, et al. AAV-mediated intramuscular delivery of myotubularin corrects the myotubular myopathy phenotype in targeted murine muscle and suggests a function in plasma membrane homeostasis Hum. Mol. Genet., July 15, 2008; 17(14): 2132 - 2143. [Abstract] [Full Text] [PDF]

				D. Sbrissa, O. C. Ikonomov, Z. Fu, T. Ijuin, J. Gruenberg, T. Takenawa, and A. Shisheva Core Protein Machinery for Mammalian Phosphatidylinositol 3,5-Bisphosphate Synthesis and Turnover That Regulates the Progression of Endosomal Transport: NOVEL SAC PHOSPHATASE JOINS THE ArPIKfyve-PIKfyve COMPLEX J. Biol. Chem., August 17, 2007; 282(33): 23878 - 23891. [Abstract] [Full Text] [PDF]

				Y. M. Ma, E. Boucrot, J. Villen, E. B. Affar, S. P. Gygi, H. G. Gottlinger, and T. Kirchhausen Targeting of AMSH to Endosomes Is Required for Epidermal Growth Factor Receptor Degradation J. Biol. Chem., March 30, 2007; 282(13): 9805 - 9812. [Abstract] [Full Text] [PDF]

				V. Tosch, H. M. Rohde, H. Tronchere, E. Zanoteli, N. Monroy, C. Kretz, N. Dondaine, B. Payrastre, J.-L. Mandel, and J. Laporte A novel PtdIns3P and PtdIns(3,5)P2 phosphatase with an inactivating variant in centronuclear myopathy Hum. Mol. Genet., November 1, 2006; 15(21): 3098 - 3106. [Abstract] [Full Text] [PDF]

				P. Choudhury, S. Srivastava, Z. Li, K. Ko, M. Albaqumi, K. Narayan, W. A. Coetzee, M. A. Lemmon, and E. Y. Skolnik Specificity of the Myotubularin Family of Phosphatidylinositol-3-phosphatase Is Determined by the PH/GRAM Domain J. Biol. Chem., October 20, 2006; 281(42): 31762 - 31769. [Abstract] [Full Text] [PDF]

				O. C. Ikonomov, D. Sbrissa, and A. Shisheva Localized PtdIns 3,5-P2 synthesis to regulate early endosome dynamics and fusion Am J Physiol Cell Physiol, August 1, 2006; 291(2): C393 - C404. [Abstract] [Full Text] [PDF]

				O. Lorenzo, S. Urbe, and M. J. Clague Systematic analysis of myotubularins: heteromeric interactions, subcellular localisation and endosomerelated functions J. Cell Sci., July 15, 2006; 119(14): 2953 - 2959. [Abstract] [Full Text] [PDF]

				S.-i. Yamashita, M. Oku, Y. Wasada, Y. Ano, and Y. Sakai PI4P-signaling pathway for the synthesis of a nascent membrane structure in selective autophagy J. Cell Biol., June 5, 2006; 173(5): 709 - 717. [Abstract] [Full Text] [PDF]

				J. E. Duex, J. J. Nau, E. J. Kauffman, and L. S. Weisman Phosphoinositide 5-Phosphatase Fig4p Is Required for both Acute Rise and Subsequent Fall in Stress-Induced Phosphatidylinositol 3,5-Bisphosphate Levels. Eukaryot. Cell, April 1, 2006; 5(4): 723 - 731. [Abstract] [Full Text] [PDF]

				J. E. Duex, F. Tang, and L. S. Weisman The Vac14p-Fig4p complex acts independently of Vac7p and couples PI3,5P2 synthesis and turnover J. Cell Biol., February 27, 2006; 172(5): 693 - 704. [Abstract] [Full Text] [PDF]

				P. Berger, I. Berger, C. Schaffitzel, K. Tersar, B. Volkmer, and U. Suter Multi-level regulation of myotubularin-related protein-2 phosphatase activity by myotubularin-related protein-13/set-binding factor-2 Hum. Mol. Genet., February 15, 2006; 15(4): 569 - 579. [Abstract] [Full Text] [PDF]

				S. Bonneick, M. Boentert, P. Berger, S. Atanasoski, N. Mantei, C. Wessig, K. V. Toyka, P. Young, and U. Suter An animal model for Charcot-Marie-Tooth disease type 4B1 Hum. Mol. Genet., December 1, 2005; 14(23): 3685 - 3695. [Abstract] [Full Text] [PDF]

				S. Noguchi, M. Fujita, K. Murayama, R. Kurokawa, and I. Nishino Gene expression analyses in X-linked myotubular myopathy Neurology, September 13, 2005; 65(5): 732 - 737. [Abstract] [Full Text] [PDF]

				F. L. Robinson and J. E. Dixon The Phosphoinositide-3-phosphatase MTMR2 Associates with MTMR13, a Membrane-associated Pseudophosphatase Also Mutated in Type 4B Charcot-Marie-Tooth Disease J. Biol. Chem., September 9, 2005; 280(36): 31699 - 31707. [Abstract] [Full Text] [PDF]

				T. Slagsvold, R. Aasland, S. Hirano, K. G. Bache, C. Raiborg, D. Trambaiolo, S. Wakatsuki, and H. Stenmark Eap45 in Mammalian ESCRT-II Binds Ubiquitin via a Phosphoinositide-interacting GLUE Domain J. Biol. Chem., May 20, 2005; 280(20): 19600 - 19606. [Abstract] [Full Text] [PDF]

				O. Lorenzo, S. Urbe, and M. J. Clague Analysis of phosphoinositide binding domain properties within the myotubularin-related protein MTMR3 J. Cell Sci., May 1, 2005; 118(9): 2005 - 2012. [Abstract] [Full Text] [PDF]

				D. Sbrissa and A. Shisheva Acquisition of Unprecedented Phosphatidylinositol 3,5-Bisphosphate Rise in Hyperosmotically Stressed 3T3-L1 Adipocytes, Mediated by ArPIKfyve-PIKfyve Pathway J. Biol. Chem., March 4, 2005; 280(9): 7883 - 7889. [Abstract] [Full Text] [PDF]

				D. Sbrissa, O. C. Ikonomov, J. Strakova, R. Dondapati, K. Mlak, R. Deeb, R. Silver, and A. Shisheva A Mammalian Ortholog of Saccharomyces cerevisiae Vac14 That Associates with and Up-Regulates PIKfyve Phosphoinositide 5-Kinase Activity Mol. Cell. Biol., December 1, 2004; 24(23): 10437 - 10447. [Abstract] [Full Text] [PDF]

				D. C. Berwick, G. C. Dell, G. I. Welsh, K. J. Heesom, I. Hers, L. M. Fletcher, F. T. Cooke, and J. M. Tavare Protein kinase B phosphorylation of PIKfyve regulates the trafficking of GLUT4 vesicles J. Cell Sci., December 1, 2004; 117(25): 5985 - 5993. [Abstract] [Full Text] [PDF]

				A. Bolino, A. Bolis, S. C. Previtali, G. Dina, S. Bussini, G. Dati, S. Amadio, U. Del Carro, D. D. Mruk, M. L. Feltri, et al. Disruption of Mtmr2 produces CMT4B1-like neuropathy with myelin outfolding and impaired spermatogenesis J. Cell Biol., November 22, 2004; 167(4): 711 - 721. [Abstract] [Full Text] [PDF]