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PMID: 12890864 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Characterization of myotubularin-related protein 7 and its binding partner, myotubularin-related protein 9.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 100 ·No. 17 ·2003-08-19 ·Pages 9768-73

Mochizuki Y, Majerus PW

Abstract

Myotubularin-related protein 7 (MTMR7) is a member of the myotubularin (MTM) family. The cDNA encoding the mouse MTMR7 contains 1,983 bp, and the predicted protein has a deduced molecular mass of 75.6 kDa. Northern and Western blot analyses showed that MTMR7 is expressed mainly in brain and mouse neuroblastoma N1E-115 cells. Recombinant MTMR7 dephosphorylated the D-3 position of phosphatidylinositol 3-phosphate and inositol 1,3-bisphosphate [Ins(1,3)P2]. The substrate specificity of MTMR7 is different than other MTM proteins in that this enzyme prefers the water-soluble substrate. Immunofluorescence showed that MTMR7 is localized in Golgi-like granules and cytosol, and subcellular fractionation showed both cytoplasmic and membrane localization of MTMR7 in N1E-115 cells. An MTMR7-binding protein was found in an anti-MTMR7 immunoprecipitate from N1E-115 cells and identified as MTM-related protein 9 (MTMR9) by tandem mass spectrometry. The coiled-coil domain of MTMR9 was sufficient for binding to MTMR7. The binding of MTMR9 increased the Ins(1,3)P2 phosphatase activity of MTMR7. Our results show that MTMR7 forms a complex with MTMR9 and dephosphorylates phosphatidylinositol 3-phosphate and Ins(1,3)P2 in neuronal cells.

MeSH Terms
Amino Acid Sequence Animals Binding Sites Brain/enzymology COS Cells Carrier Proteins/chemistry,genetics,metabolism Cell Line DNA, Complementary/genetics Humans In Vitro Techniques Inositol Phosphates/metabolism Mice Molecular Sequence Data Phosphatidylinositol Phosphates/metabolism Phosphoric Monoester Hydrolases/chemistry,genetics,metabolism Protein Binding Protein Structure, Tertiary Protein Tyrosine Phosphatases/genetics,metabolism Protein Tyrosine Phosphatases, Non-Receptor Recombinant Proteins/chemistry,genetics,metabolism Substrate Specificity Tissue Distribution
Chemicals
Carrier Proteins DNA, Complementary Inositol Phosphates Phosphatidylinositol Phosphates Recombinant Proteins phosphatidylinositol 3-phosphate inositol 1,3-bisphosphate Phosphoric Monoester Hydrolases Mtmr7 protein, mouse Mtmr9 protein, mouse Protein Tyrosine Phosphatases Protein Tyrosine Phosphatases, Non-Receptor myotubularin
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Mochizuki Yasuhiro
Washington University School of Medicine, Department of Internal Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
Majerus Philip W
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.1333958100
Published
2003-08-19
Epub
2003-00-30
Pages
9768-73
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC187840
Subset
IM
Grants
NHLBI NIH HHS · R01 HL016634 · United States
NHLBI NIH HHS · HL 16634 · United States
NHLBI NIH HHS · HL 55772 · United States
External Links
PubMed source DOI: 10.1073/pnas.1333958100 PMC Full Text View journal details
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