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Two-pore channel 1 interacts with citron kinase, regulating completion of cytokinesis.

ABSTRACT: Two-pore channels (TPC1, 2, and 3) are recently identified endolysosmal ion channels, but remain poorly characterized. In this study, we show for the first time a role for TPC1 in cytokinesis, the final step in cell division. HEK 293 T-REx cells inducibly overexpressing TPC1 demonstrated a lack of proliferation accompanied by multinucleation and an increase in G2/M cycling cells. Increased TPC1 was associated with a concomitant accumulation of active RhoGTP and a decrease in phosphorylated myosin light chain (MLC). Finally, we demonstrated a novel interaction between TPC1 and citron kinase (CIT). These results identify TPC1 as a central component of cytokinetic control, specifically during abscission, and introduce a means by which the endolysosomal system may play an active role in this process.

SUBMITTER: Horton JS

PROVIDER: S-EPMC4594595 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Two-pore channel 1 interacts with citron kinase, regulating completion of cytokinesis.

Horton Jaime S JS Wakano Clay T CT Speck Mark M Stokes Alexander J AJ

Channels (Austin, Tex.) 20150101 1

Two-pore channels (TPC1, 2, and 3) are recently identified endolysosmal ion channels, but remain poorly characterized. In this study, we show for the first time a role for TPC1 in cytokinesis, the final step in cell division. HEK 293 T-REx cells inducibly overexpressing TPC1 demonstrated a lack of proliferation accompanied by multinucleation and an increase in G2/M cycling cells. Increased TPC1 was associated with a concomitant accumulation of active RhoGTP and a decrease in phosphorylated myosi ...[more]

PMID: 25665131

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p27(Kip1) controls cytokinesis via the regulation of citron kinase activation.

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Drosophila citron kinase is required for the final steps of cytokinesis.

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Lestaurtinib inhibits Citron kinase activity and medulloblastoma growth through induction of DNA damage, apoptosis and cytokinesis failure.

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| S-EPMC10315473 | biostudies-literature

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