Abstract
Asymmetric cell division generates cell diversity and contributes to cellular aging and rejuvenation. Here, we review the molecular mechanisms enabling budding yeast to recognize spindle pole bodies (SPB, centrosome equivalent) based on their age, and guide their non-random mitotic segregation: SPB inheritance requires the distinction of old from new SPBs and is regulated by the SPB-inheritance network (SPIN) and the mitotic exit network (MEN). The SPIN marks the pre-existing SPB as old and the MEN recognizes these marks translating them into spindle orientation. We next revisit other molecules and structures that partition depending on their age rather than their abundance at mitosis as, for example, DNA, centrosomes, mitochondria, and histones in yeast and other systems. The recurrence of this differential behavior suggests a functional significance for numerous cell types, which we then discuss. We conclude that non-random segregation may facilitate asymmetric cell fate determination and thereby indirectly aging and rejuvenation. Also see the video abstract here: https://youtu.be/1sQ4rAomnWY.
Highlights
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Asymmetric cell division generates cell diversity and contributes to cellular we focus on ubiquitous molecules and aging and rejuvenation
We review the molecular mechanisms enabling budding yeast to recognize spindle pole bodies (SPB, centrosome equivalent) based on their age, and guide their non-random mitotic segregation: SPB inheritance requires the distinction of old from new SPBs and is regulated by structures partitioning asymmetrically not according to mass but to their age (Figure 1)
Summary
It likely involves the phosphorylation of an evolutionarily conserved residue, Y362, of γ-tubulin.[32] the microtubule organization capacity of SPBs is not intrinsically determined by their age and maturation but rather by regulatory cues provided by the cell cortex This process of microtubule formation does not explain how cells reliably orient the old SPB toward the bud. In these cells Kar remains associated with the old SPB unlike microtubules, which accumulate on the budproximal SPB irrespective of its age.[24] the SPB controls Kar localization in an age-dependent manner explaining why the old SPB orients toward the bud and, forms longer microtubules These data support the model that SPBs direct their own inheritance by controlling Kar distribution. SPB inheritance requires that the cell distinguishes old from new SPBs, a process that we term SPB specification, and is regulated by the MEN
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