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Interaction between human myotubularin proteins MTMR6 and MTMR9
Author(s) -
Chang ShaoChun,
Zou Jun,
Majerus Philip W.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a484-b
Subject(s) - phosphatidylinositol , phosphatidylinositol 4,5 bisphosphate , biochemistry , binding site , phosphatase , enzyme , in vitro , chemistry , plasma protein binding , kinase
Human MTMR6 and MTMR9 are members of a large family of phosphatidylinositol 3‐phosphatases (currently 14 members identified) associated with myotubular myopathy and Charcot Marie Tooth syndrome. MTMR6 is enzymatically active with phosphatidylinositol‐3‐phosphate and phosphatidylinositol‐3,5‐bisphosphate as substrates; MTMR9 is enzymatically inactive. We demonstrate the following: 1. MTMR6 binds to MTMR9 by in vitro GST‐pull‐down assay; 2. MTMR6 binds to monophosphorylated phosphatidylinositols at the 3, 4, and 5 positions and to a lesser extend to phosphatidylinositol‐3,5‐bisphosphate by PIP‐Strip binding assay; 3. MTMR9 has no significant lipid binding; 4. interaction between MTMR6 and MTMR9 increased phosphatidylinositol binding of MTMR6 by PIP‐Array binding assay; and 5. MTMR6 enzymatic activity is increased 13‐ to 20‐fold in the presence of MTMR9, and this activity is independently increased by phosphatidylinositol‐4‐phosphate (50%) and phosphatidylinositol‐5‐phosphate (100%). We conclude that MTMR9 significantly increases the enzymatic activity and the lipid binding affinity of MTMR6. This research was supported by National Institutes of Health grants RO1‐HL16634 and American Heart Association grant 0475014N