title: 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.
authors: a Laboratory of Experimental Medicine; John A. Burns School of Medicine ; University of Hawaii ; Honolulu , HI USA.
authors: Jaime S
authors: JS
authors: Horton
authors: Clay T
authors: CT
authors: Wakano
authors: Mark
authors: M
authors: Speck
authors: Alexander J
authors: AJ
authors: Stokes
mesh_terms: D015220:Calcium Channels / Q000737:chemistry / Q000378:metabolism*; D049109:Cell Proliferation; D002478:Cells, Cultured; D048749:Cytokinesis; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D000097903:Two-Pore Channels
chemical_list: D015220:Calcium Channels; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; C407357:TPCN1 protein, human; D000097903:Two-Pore Channels; C530224:TPCN2 protein, human; C115635:citron-kinase
keywords: 2-pore channel; MLC; Rho; TPC; abscission; autophagy; cancer; cell cycle; citron kinase; cytokinesis; lysosome; multinucleation; polyploidy; tumor