CMT Mutations and Myotubularin phosphatases: policing 3-phosphoinositides

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Trends Cell Biol. 2006 Jul 5

Myotubularin phosphatases: policing 3-phosphoinositides.

FL, Dixon JE.

Departments of Pharmacology, Cellular and Molecular Medicine, and

Chemistry and Biochemistry, School of Medicine, University of

California San Diego, Leichtag Biomedical Research Building, Rm. 284,

9500 Gilman Drive, La Jolla, CA 92093-0721, USA.

In eukaryotic cells, phosphatidylinositol is subject to differential

phosphorylation, resulting in the production of seven distinct

phosphatidylinositol phosphates, often referred to as

phosphoinositides (PIs). PIs have numerous distinct roles in cellular

regulation and membrane trafficking. Recently, myotubularin family PI

3-phosphatases have emerged as key regulators of phosphatidylinositol

3-phosphate and phosphatidylinositol 3,5-bisphosphate, two PIs that

regulate traffic within the endosomal-lysosomal pathway.

Mutations in several myotubularin genes lead to myotubular myopathy

and Charcot-Marie-Tooth peripheral neuropathy. Strikingly, nearly

half of the members of the human myotubularin family appear to be

catalytically inactive. Several inactive myotubularins have essential

functions in mammals. Recent work in mammalian cells and model

organisms is shedding light on the roles of myotubularins in membrane

traffic.