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The PtdIns3P phosphatase myotubularin is a cytoplasmic protein that also localizes to Rac1-inducible plasma membrane ruffles

Jocelyn Laporte, Francois Blondeau^*, Anne Gansmuller, Yves Lutz, Jean-Luc Vonesch and Jean-Louis Mandel

Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, 1 rue Laurent Fries, BP 10142, 67404 Illkirch Cedex, CU de Strasbourg, France
^* Present address: McGill Cancer Centre, McGill University, 3655 Promenade Sir William Osler, McIntyre Medical Sciences Building, Room 702, Montreal, Québec, Canada H3G 1Y6
Present address: INSERM U 338, Centre de Neurochimie, 5 rue Blaise Pascal, 67084 Strasbourg, France

Authors for correspondence (e-mail: mtm{at}titus.u-strasbg.fr )

Accepted 1 May 2002

Myotubularin, the phosphatase mutated in X-linked myotubular myopathy, was shown to dephosphorylate phosphatidylinositol 3-monophosphate (PtdIns3P) and was also reported to interact with nuclear transcriptional regulators from the trithorax family. We have characterized a panel of specific antibodies and investigated the subcellular localization of myotubularin. Myotubularin is not detected in the nucleus, and localizes mostly as a dense cytoplasmic network. Overexpression of myotubularin does not detectably affect vesicle trafficking in the mammalian cells investigated, in contrast to previous observations in yeast models. Both mutation of a key aspartate residue of myotubularin and dominant activation of Rac1 GTPase lead to the recruitment of myotubularin to specific plasma membrane domains. Localization to Rac1-induced ruffles is dependent on the presence of a domain highly conserved in the myotubularin family (that we named RID). We thus propose that myotubularin may dephosphorylate a subpool of PtdIns3P (or another related substrate) at the plasma membrane.

Key words: Myotubularin, Myotubular myopathy, Phosphatidylinositol 3-monophosphate, Membrane trafficking, Rac GTPase, Phosphatase, RID domain

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