Centrosomal, Arp2/3 complex-dependent actin assembly is required for proper mitotic spindle formation and chromosome congression

• Applicant: Professor Dr. Robert Grosse
• Subject Area: Cell Biology
• Term: from 2019 to 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 427436068

Cytoskeletal crosstalk between actin filaments and microtubules governs the assembly of various cellular structures, such as filopodia or cilia. After disassembly of interphasic structures during mitotic entry, centrosomes operating as microtubule-organizing centers (MTOCs) are of special interest as they propagate the formation of the mitotic spindle, which aligns individual chromosomes to the metaphase plate, a process termed chromosome congression. Here, we aim to investigate actin filament assembly that we find spatially defined at the centrosome contemporaneously with forming spindle microtubules. These actin filaments appear immediately after nuclear envelope breakdown (NEBD) and remain discernable during the course of mitotic spindle formation. Our data show that pharmacological Arp2/3 inhibition at mitotic entry decreases spindle actin and subsequently impairs mitotic spindle formation, which results in severely disorganized chromosome congression and ultimately cell death in non-transformed cells. the aim of this proposal is to further define and elucidate the molecular events and mechanisms during this process. These findings shall provide a better understanding of actin dynamics during cell division and its potential role for the maintenance of genomic integrity during mitosis.

• DFG Programme: Research Grants