Misshapen-like kinase 1 (MINK1) Is a Novel Component of Striatin-interacting Phosphatase and Kinase (STRIPAK) and Is Required for the Completion of Cytokinesis

Background: Cytokinesis is regulated by phosphorylation and dephosphorylation of proteins. Results: MINK1 associated with STRN4, a regulatory subunit of PP2A, and depletion of either protein inhibited completion of cytokinesis. Conclusion: MINK1 and STRN4 are required for abscission, the final stage...

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Bibliographic Details
Published in:The Journal of biological chemistry 2012-07, Vol.287 (30), p.25019-25029
Main Authors: Hyodo, Toshinori, Ito, Satoko, Hasegawa, Hitoki, Asano, Eri, Maeda, Masao, Urano, Takeshi, Takahashi, Masahide, Hamaguchi, Michinari, Senga, Takeshi
Format: Article
Language:English
Subjects:
Calmodulin-Binding Proteins - genetics
Calmodulin-Binding Proteins - metabolism
Cell Biology
Cell Cycle
Cell Division
Cytokinesis
Cytokinesis - physiology
Gene Knockdown Techniques
HeLa Cells
Humans
Multienzyme Complexes - genetics
Multienzyme Complexes - metabolism
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Protein Phosphatase 2 - genetics
Protein Phosphatase 2 - metabolism
Protein-Serine-Threonine Kinases - genetics
Protein-Serine-Threonine Kinases - metabolism
Serine Threonine Protein Kinase
Serine Threonine Protein Phosphatase
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Summary:Background: Cytokinesis is regulated by phosphorylation and dephosphorylation of proteins. Results: MINK1 associated with STRN4, a regulatory subunit of PP2A, and depletion of either protein inhibited completion of cytokinesis. Conclusion: MINK1 and STRN4 are required for abscission, the final stage of cytokinesis. Significance: Our study reveals novel regulatory mechanisms for abscission. Cytokinesis is initiated by constriction of the cleavage furrow and terminated by abscission of the intercellular bridge that connects two separating daughter cells. The complicated processes of cytokinesis are coordinated by phosphorylation and dephosphorylation mediated by protein kinases and phosphatases. Mammalian Misshapen-like kinase 1 (MINK1) is a member of the germinal center kinases and is known to regulate cytoskeletal organization and oncogene-induced cell senescence. To search for novel regulators of cytokinesis, we performed a screen using a library of siRNAs and found that MINK1 was essential for cytokinesis. Time-lapse analysis revealed that MINK1-depleted cells were able to initiate furrowing but that abscission was disrupted. STRN4 (Zinedin) is a regulatory subunit of protein phosphatase 2A (PP2A) and was recently shown to be a component of a novel protein complex called striatin-interacting phosphatase and kinase (STRIPAK). Mass spectrometry analysis showed that MINK1 was a component of STRIPAK and that MINK1 directly interacted with STRN4. Similar to MINK1 depletion, STRN4-knockdown induced multinucleated cells and inhibited the completion of abscission. In addition, STRN4 reduced MINK1 activity in the presence of catalytic and structural subunits of PP2A. Our study identifies a novel regulatory network of protein kinases and phosphatases that regulate the completion of abscission.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M112.372342