Local actin nucleation tunes centrosomal microtubule nucleation during passage through mitosis

Abstract

Cells going through mitosis undergo precisely timed changes in cell shape and organisation, which serve to ensure the fair partitioning of cellular components into the two daughter cells. These structural changes are driven by changes in actin filament and microtubule dynamics and organisation. While most evidence suggests that the two cytoskeletal systems are remodelled in parallel during mitosis, recent work in interphase cells has implicated the centrosome in both microtubule and actin nucleation, suggesting the potential for regulatory crosstalk between the two systems. Here, by using both in vitro and in vivo assays to study centrosomal actin nucleation as cells pass through mitosis, we show that mitotic exit is accompanied by a burst in cytoplasmic actin filament formation that depends on WASH and the Arp2/3 complex. This leads to the accumulation of actin around centrosomes as cells enter anaphase and to a corresponding reduction in the density of centrosomal microtubules. Taken together, these data suggest that the mitotic regulation of centrosomal WASH and the Arp2/3 complex controls local actin nucleation, which may function to tune the levels of centrosomal microtubules during passage through mitosis.

Centrosome–nuclear axis repositioning drives the assembly of a bipolar spindle scaffold to ensure mitotic fidelity

“…Treatment with CK666 during prophase increased the number of microtubule growths, as well as microtubule speed and length, when compared with controls ( Figure 6, H–L , *** p < 0.001), in line with the microtubule-destabilizing effect of branched actin networks ( Colin et al. , 2018 ; Farina et al. , 2019 ; Inoue et al.…”

“…, 2013 ) or mitotic cortex structure ( Chugh et al. , 2017 ), its activity was recently proposed to assist in microtubule remodeling at mitotic exit ( Farina et al. , 2019 ).…”

“…Moreover, actin localizes to centrosomes in an Arp2/3-dependent manner ( Farina et al. , 2016 , 2019 ) to assist in microtubule network remodeling ( Farina et al. , 2019 ; Inoue et al.…”

The actin regulator profilin 1 is functionally associated with the mammalian centrosome

“…Profilin-actin serves as source of actin for microfilament polymerization and as such co-operates with actin nucleation and elongation promoting proteins (26,27,28,29,33,39,40). A possible scenario is therefore that the loss of profilin results in less of actin polymerization in the centrosomal region in analogy with what was recently reported for the cell edge (41); as a consequence, less of steric hindrance (8,42) would reduce a possible space constrain for enhanced de novo microtubule nucleation. Alternatively, because actin is a structural component of functional γTuRCs (22,23,24), centrosomal profilin may tune the availability of actin for γTuRC.…”

Artificially decreasing cortical tension generates aneuploidy in mouse oocytes

“…It is usually thought that changes in cortical tension are transmitted mechanically to the MT spindle. In particular, F-actin is known to impact MT architecture and dynamics, potentially acting on chromosome behavior in oocytes and other systems 9,[34][35][36][37][38] . There is also evidence showing that myosin-II is involved in MT functions and thus potentially in chromosome behavior.…”