Misshapen-like kinase 1 (MINK1) is a novel component of striatin-interacting phosphatase and kinase (STRIPAK) and is required for the completion of cytokinesis.
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.
Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
Toshinori
T
Hyodo
Satoko
S
Ito
Hitoki
H
Hasegawa
Eri
E
Asano
Masao
M
Maeda
Takeshi
T
Urano
Masahide
M
Takahashi
Michinari
M
Hamaguchi
Takeshi
T
Senga
D002148:Calmodulin-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D048749:Cytokinesis / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*
D002148:Calmodulin-Binding Proteins; D009097:Multienzyme Complexes; D009419:Nerve Tissue Proteins; C411649:zinedin; C497353:MINK1 protein, human; D017346:Protein Serine-Threonine Kinases; C517189:PPP2CA protein, human; D054648:Protein Phosphatase 2