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

J Cell Sci. 2002 Aug 1;115(Pt 15):3105-17. doi: 10.1242/jcs.115.15.3105.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies
  • Cell Compartmentation / genetics
  • Cell Surface Extensions / enzymology*
  • Cell Surface Extensions / ultrastructure
  • Cytoplasm / enzymology*
  • Cytoplasmic Vesicles / metabolism
  • Cytoplasmic Vesicles / ultrastructure
  • Eukaryotic Cells / enzymology*
  • Eukaryotic Cells / ultrastructure
  • Fluorescent Antibody Technique
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Confocal
  • Mutation / genetics
  • Myopathies, Structural, Congenital / enzymology*
  • Myopathies, Structural, Congenital / genetics
  • Myopathies, Structural, Congenital / physiopathology
  • Phosphatidylinositol Phosphates / metabolism*
  • Protein Structure, Tertiary / genetics
  • Protein Transport / genetics
  • Protein Tyrosine Phosphatases / deficiency*
  • Protein Tyrosine Phosphatases / genetics
  • Protein Tyrosine Phosphatases, Non-Receptor
  • rac1 GTP-Binding Protein / genetics
  • rac1 GTP-Binding Protein / metabolism*

Substances

  • Antibodies
  • Phosphatidylinositol Phosphates
  • Protein Tyrosine Phosphatases
  • Protein Tyrosine Phosphatases, Non-Receptor
  • myotubularin
  • rac1 GTP-Binding Protein