Abstract:SummaryThe terminal stage of cytokinesis -a process termed abscission -is the severing of the thin intercellular bridge that connects the two daughter cells. Recent work provides new insight into the mechanism by which this microtubule-dense membrane bridge is resolved, and highlights important roles for multi-protein assemblies in different facets of abscission. These include the endosomal sorting complex required for transport (ESCRT), which appears to have a decisive role in the final scission event, and ve… Show more
“…55 Abscission is known to be carried out by the combination of several events including vesicle trafficking, microtubule remodeling and membrane deformation. [56][57][58] Cytokinesis failure leads to centrosome amplification and production of tetraploid cells, introducing chromosomal instability and setting the stage for tumor cell development. 23,32 Expression of TPC1 was significantly upregulated in a human protein array of tumor tissue compared to normal tissue, suggesting that dysregulated TPC1 expression may contribute to the aberrant cell division prominent in many cancers.…”
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.
“…55 Abscission is known to be carried out by the combination of several events including vesicle trafficking, microtubule remodeling and membrane deformation. [56][57][58] Cytokinesis failure leads to centrosome amplification and production of tetraploid cells, introducing chromosomal instability and setting the stage for tumor cell development. 23,32 Expression of TPC1 was significantly upregulated in a human protein array of tumor tissue compared to normal tissue, suggesting that dysregulated TPC1 expression may contribute to the aberrant cell division prominent in many cancers.…”
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.
“…Abscission is the final separation of the cytoplasms and plasma membranes of the two daughter cells [reviewed recently by Neto and Gould, 2011]. It is thought to be accomplished by localized removal of midbody microtubules and by vesicle delivery and fusion.…”
Polar body cytokinesis is the physical separation of a small polar body from a larger oocyte or ovum. This maternal meiotic division shares many similarities with mitotic and spermatogenic cytokinesis, but there are several distinctions, which will be discussed in this review. We synthesize results from many different model species, including those popular for their genetics and several that are more obscure in modern cell biology. The site of polar body division is determined before anaphase, by the eccentric, cortically associated meiotic spindle. Depending on the species, either the actin or microtubule cytoskeleton is required for spindle anchoring. Chromatin is necessary and sufficient to elicit differentiation of the associated cortex, via Ran-based signaling. The midzone of the anaphase spindle serves as a hub for regulatory complexes that elicit Rho activation, and ultimately actomyosin contractile ring assembly and contraction. Polar body cytokinesis uniquely requires another Rho family GTPase, Cdc42, for dynamic reorganization of the polar cortex. This is perhaps due to the considerable asymmetry of this division, wherein the polar body and the oocyte/ovum have distinct fates and very different sizes. Thus, maternal meiotic cytokinesis appears to occur via simultaneous polar relaxation and equatorial contraction, since the polar body is extruded from the spherical oocyte through the nascent contractile ring. As such, polar body cytokinesis is an interesting and important variation on the theme of cell division. V C 2012 Wiley Periodicals, Inc
“…In the meantime, it is now recognized as being ubiquitously required for exocytic events in all eukaryotic cells (Heider and Munson, 2012). The exocyst complex also facilitates a number of other membrane fusion processes such as cytokinesis (Neto and Gould, 2011;Rybak et al, 2014) and autophagy (Bodemann et al, 2011). Plants also have an exocyst complex, and there are a number of papers implicating its role in secretion (Kulich et al, 2010;Li et al, 2013;Safavian and Goring, 2013;Cole et al, 2014).…”
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