Identification of Myotubularin As the Lipid Phosphatase Catalytic Subunit Associated with the 3-Phosphatase Adapter Protein, 3-PAP
Identification of myotubularin as the lipid phosphatase catalytic subunit associated with the 3-phosphatase adapter protein, 3-PAP Harshal H. Nandurkar*†, Meredith Layton‡, Jocelyn Laporte§, Carly Selan*, Lisa Corcoran*¶, Kevin K. Caldwellʈ, Yasuhiro Mochizuki**, Philip W. Majerus**, and Christina A. Mitchell¶ *St. Vincent’s Hospital, 3065 Melbourne, Australia; ‡Ludwig Institute of Medical Research, 3050 Parkville, Australia; §Institute of Genetics and Molecular and Cellular Biology, 67404 Illkirch Cedex, France; ¶Department of Biochemistry and Molecular Biology, Monash University, 3068 Clayton, Australia; ʈDepartment of Neuroscience, University of New Mexico, Albuquerque, NM 87131; and **Department of Haematology, Washington University Medical School, St. Louis, MO 63110 Contributed by Philip W. Majerus, May 21, 2003 Myotubularin is a dual-specific phosphatase that dephosphory- syndrome, a hereditary demyelinating peripheral neuropathy lates phosphatidylinositol 3-phosphate and phosphatidylinositol (17, 18). (3,5)-bisphosphate. Mutations in myotubularin result in the human The catalytically inactive myotubularin family members in- disease X-linked myotubular myopathy, characterized by persis- clude SET-binding factor 1 (MTMR5), LIP-STYX (MTMR9), tence of muscle fibers that retain an immature phenotype. We have MTMR10, the 3-phosphatase adapter protein (3-PAP) previously reported the identification of the 3-phosphatase (MTMR12), and MTMR13 (SET-binding factor 2) (7, 14–16, 19, adapter protein (3-PAP), a catalytically inactive member of the 20). The function of these catalytically inactive phosphatases is myotubularin gene family, which coprecipitates lipid phosphati- unknown. Very recently, mutations in MTMR13 have been dylinositol 3-phosphate-3-phosphatase activity from lysates of described in type 4B2 Charcot Marie Tooth syndrome (19, 20). human platelets. We have now identified myotubularin as the Also, male mice deficient in SET-binding factor 1 are azoosper- catalytically active 3-phosphatase subunit interacting with 3-PAP.
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