Centrosomal Actin Assembly is Required for Proper Mitotic Spindle Formation and Chromosome Congression

Abstract

Cytoskeletal crosstalk between actin filaments and microtubules is a common mechanism governing the assembly of cellular structures, i.e. during filopodia formation or cilia organisation. However, potential actin-microtubule interactions during mammalian cell divisions are less well understood. At mitotic entry, centrosomes propagate the formation of the mitotic spindle thereby aligning individual chromosomes to the metaphase plate, a process coined chromosome congression. Here, we identify actin filament assembly spatially defined at centrosomes contemporaneously with forming spindle microtubules during prometaphase. We show that pharmacological Arp2/3 complex inhibition as well as overexpression of the Arp2/3 complex inhibitory protein Arpin decreased spindle actin formation. As a consequence, mitotic spindle formation is impaired, which resulted in disorganized chromosome congression and ultimately mitotic defects in non-transformed cells. Thus, centrosomal Arp2/3 complex activity plays a role for maintenance of genomic integrity during mitosis.