Local actin nucleation tunes centrosomal microtubule nucleation during passage through mitosis

• Published in: The EMBO journal Vol. 38; no. 11
• Main Authors: Farina, Francesca, Ramkumar, Nitya, Brown, Louise, Samandar Eweis, Dureen, Anstatt, Jannis, Waring, Thomas, Bithell, Jessica, Scita, Giorgio, Thery, Manuel, Blanchoin, Laurent, Zech, Tobias, Baum, Buzz
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.06.2019; Springer Nature B.V; EMBO Press; John Wiley and Sons Inc
• Subjects: Actin; Actin Cytoskeleton - metabolism; Actins - metabolism; Anaphase; Arp2/3 complex; Cell size; Cells, Cultured; Cellular Biology; Cellular structure; centrosomal actin; Centrosome - metabolism; Centrosomes; Crosstalk; Cytoskeleton; Cytoskeleton - metabolism; Density; EMBO05; EMBO06; Filaments; HeLa Cells; Humans; In vivo methods and tests; Interphase; Interphase - physiology; Jurkat Cells; Life Sciences; Microtubules; Microtubules - metabolism; Mitosis; Mitosis - physiology; Nucleation; Protein Multimerization - physiology; Reduction; WASH complex; Arp2/3 complex; centrosomal actin; WASH complex; mitosis; WASH complex Subject Categories Cell Adhesion; Cell Cycle; Polarity & Cytoskeleton
• ISSN: 0261-4189; 1460-2075; 1460-2075
• DOI: 10.15252/embj.201899843

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. Synopsis Centrosomes, the main interphase microtubule‐organizing centers, were recently found to also nucleate actin filaments. Here, local actin nucleation is observed in anaphase, tuning centrosomal microtubule nucleation as cells passage through mitosis. Centrosomes function as both actin‐ and microtubule‐organizing centers during mitotic exit. Actin transiently accumulates around centrosomes at early anaphase. In vitro reconstitution assays with isolated centrosomes show a burst in actin filament formation at early anaphase. Anaphase actin filament formation depends on Arp2/3 and WASH complex activity. The anaphase actin burst around centrosomes is accompanied by reduction in microtubule density suggesting cross‐talk between the two systems. Graphical Abstract Centrosomes organize both microtubule and actin filaments during mitosis, with a transient burst of actin nucleation in anaphase correlating with reduced microtubule density.