4/2/2023 0 Comments Spindle microtubulesCentrosomes are also differentially inherited during the division of mouse radial glia progenitors and human neuroblastoma cells ( Conduit and Raff, 2010 Izumi and Kaneko, 2012 Rebollo et al., 2007 Wang et al., 2009). Analogously, centrosomin ( Cnn), the Drosophila CDK5RAP2 homolog, is required for asymmetric centrosome inheritance in germline stem cells (GSCs) and neuroblasts ( Conduit and Raff, 2010 Yamashita et al., 2007). Spc72, a member of this family, asymmetrically localizes to the SPB that enters the daughter cell during budding yeast division, and is required for establishing the differential SPB inheritance pattern during mitosis ( Juanes et al., 2013). However, many proteins involved in this process are evolutionarily conserved an illustrative example is the CDK5RAP2 family of γ-tubulin complex receptors (γ-TuCRs). The precise mechanisms that orchestrate the differential distribution of old and new spindle MTOCs during asymmetric cell divisions are still not completely understood. We have recently demonstrated that the asymmetric SPB inheritance pattern is essential for maintaining the full replicative lifespan of budding yeast cells ( Manzano-López et al., 2019). ![]() Originally described in the budding yeast Saccharomyces cerevisiae ( Pereira et al., 2001), this phenomenon was later also documented in cells from other organisms, including humans ( Izumi and Kaneko, 2012 Pelletier and Yamashita, 2012 Reina and Gonzalez, 2014). The old and new spindle MTOCs can be differentially distributed between the mother and daughter cells during certain asymmetric divisions ( Lengefeld and Barral, 2018 Pelletier and Yamashita, 2012 Reina and Gonzalez, 2014). ![]() After duplication early in the cell cycle, spindle MTOCs exhibit inherent asymmetry, with pre-existent (‘old’) and newly generated (‘new’) MTOCs differing in terms of composition, structure, and age ( Nigg and Stearns, 2011 Pelletier and Yamashita, 2012). These MTOCs, known as centrosomes in animal cells or spindle pole bodies (SPBs) in budding yeast ( Conduit et al., 2015 Ito and Bettencourt-Dias, 2018 Kilmartin, 2014), nucleate interpolar microtubules that provide stability to the spindle, kinetochore microtubules that anchor the chromosomes to enable their segregation, and astral or cytoplasmic microtubules that position the spindle relative to the cytokinesis plane ( Prosser and Pelletier, 2017 Winey and Bloom, 2012). A critical component of this system is the mitotic spindle, a bipolar array of microtubules that originate from microtubule-organizing centers (MTOCs) located at either pole. To maintain correct ploidy through mitosis, cells have developed an elaborate molecular machinery that facilitates chromosomal segregation and surveillance mechanisms that preserve DNA integrity and ensure even distribution of the duplicated genome during the process. We demonstrate that the Plk1 homolog Cdc5 acts as a molecular timer that facilitates the timely and sequential recruitment of two key determinants of spindle MTOCs distribution, that is the γ-tubulin complex receptor Spc72 and the protein Kar9, and establishes the fate of these structures, safeguarding their asymmetric inheritance during Saccharomyces cerevisiae mitosis. Here, we expand the repertoire of functions Polo-like kinase family members fulfill in regulating pivotal cell cycle processes. Problems with establishing predetermined spindle MTOC inheritance patterns during stem cell division have been associated with accelerated cellular aging and the development of both cancer and neurodegenerative disorders. ![]() ![]() After duplication, spindle MTOCs can be differentially inherited during asymmetric cell division in organisms ranging from yeast to humans. The microtubules that form the mitotic spindle originate from microtubule-organizing centers (MTOCs) located at either pole.
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