Journal
JOURNAL OF CELL SCIENCE
Volume 118, Issue 9, Pages 2005-2012Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02325
Keywords
myotubularin; PH domain; FYVE domain; phosphoinositides; phosphatase; Golgi
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Funding
- Wellcome Trust Funding Source: Medline
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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.
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