Publications

• Characterization of MTMR3. an inositol lipid 3-phosphatase with novel substrate specificity.

  Walker D.M., Urbe S., Dove S.K., Tenza D., Raposo G., Clague M.J.

  Inositol lipids play key roles in many fundamental cellular processes that include growth, cell survival, motility, and membrane trafficking. Recent studies on the PTEN and Myotubularin proteins have underscored the importance of inositol lipid 3-phosphatases in cell function. Inactivating mutatio ... >> More

  Inositol lipids play key roles in many fundamental cellular processes that include growth, cell survival, motility, and membrane trafficking. Recent studies on the PTEN and Myotubularin proteins have underscored the importance of inositol lipid 3-phosphatases in cell function. Inactivating mutations in the genes encoding PTEN and Myotubularin are key steps in the progression of some cancers and in the onset of X-linked myotubular myopathy, respectively. Myotubularin-related protein 3 (MTMR3) shows extensive homology to Myotubularin, including the catalytic domain, but additionally possesses a C-terminal extension that includes a FYVE domain. We show that MTMR3 is an inositol lipid 3-phosphatase, with a so-far-unique substrate specificity. It is able to hydrolyze PtdIns3P and PtdIns3,5P2, both in vitro and when heterologously expressed in S. cerevisiae, and to thereby provide the first clearly defined route for the cellular production of PtdIns5P. Overexpression of a catalytically dead MTMR3 (C413S) in mammalian cells induces a striking formation of vacuolar compartments that enclose membranous structures that are highly concentrated in mutant proteins. << Less

  Curr. Biol. 11:1600-1605(2001) [PubMed] [EuropePMC]

  This publication is cited by 3 other entries.

• Analysis of phosphoinositide binding domain properties within the myotubularin-related protein MTMR3.

  Lorenzo O., Urbe S., Clague M.J.

  The myotubularins are a large family of phosphoinositide-specific phosphatases with substrate specificity for PtdIns3P and PtdIns(3,5)P(2). In addition to an N-terminal PH-GRAM (PH-G) domain and a signature catalytic domain shared with other family members, MTMR3 contains a C-terminal FYVE domain. ... >> More

  The myotubularins are a large family of phosphoinositide-specific phosphatases with substrate specificity for PtdIns3P and PtdIns(3,5)P(2). In addition to an N-terminal PH-GRAM (PH-G) domain and a signature catalytic domain shared with other family members, MTMR3 contains a C-terminal FYVE domain. We show that the FYVE domain of MTMR3 is atypical in that it neither confers endosomal localisation nor binds to the lipid PtdIns3P. Furthermore the FYVE domain is not required for in vitro enzyme activity of MTMR3. In contrast, the PH-GRAM domain is able to bind to phosphoinositide lipids, of which the allosteric regulator PtdIns5P is the preferred partner. Consequently, generation of PtdIns5P at the plasma membrane by ectopic expression of the bacterial phosphatase IpgD leads to a translocation of MTMR3 that requires the PH-G domain. Deletion of the PH-G domain leads to loss of activity of MTMR3 in vitro, and surprisingly, when combined with an active site mutation, accumulates the protein on the Golgi complex. << Less

  J Cell Sci 118:2005-2012(2005) [PubMed] [EuropePMC]

  This publication is cited by 1 other entry.