Fascetto Interacting Protein (FIP) Regulates Fascetto (PRC1) to Ensure Proper Cytokinesis and Ploidy

Abstract

Cell division is critical for development, organ growth, and tissue repair. The later stages of cell division include the formation of the microtubule (MT)-rich central spindle in anaphase, which is required to properly define the cell equator, guide the assembly of the acto-myosin contractile ring, and ultimately ensure complete separation and isolation of the two daughter cells via abscission. Much is known about the molecular machinery that forms the central spindle, including proteins needed to generate the antiparallel overlapping interzonal MTs. One critical protein that has garnered great attention is Protein Regulator of Cytokinesis 1 (PRC1), or Fascetto (Feo) in Drosophila, which forms a homodimer to crosslink interzonal MTs, ensuring proper central spindle formation and cytokinesis. Here, we report on a new direct protein interactor and regulator of Feo we named Fascetto Interacting Protein (FIP). Loss of FIP results in a significant reduction in Feo localization, rapid disassembly of interzonal MTs, and several cytokinesis defects. Simultaneous reduction in Feo and FIP results in tumor-like, DNA-filled masses in the brain. In aggregate our data show that FIP functions upstream of, and acts directly on, Feo to ensure fully accurate cell division.

Traip Mitotic Function Controls Brain Size

“…In mammalian NPCs, polypoidy and binucleation can cause G1 arrest and apoptosis (Aylon and Oren, 2011; Storchova and Kuffer, 2008). In Drosophila , neurons can become polyploid in response to DNA damage (Nandakumar et al, 2020), and NBs can become massively polyploid in some mutants (Poulton et al, 2017; Swider et al, 2019), suggesting that, even though polyploidy may be better tolerated in flies, polyploid NBs are unlikely to successfully complete additional mitoses. We infer the existence of traip - aneuploid MB-NBs which produce a wide range of daughter KC numbers, suggesting that traip - generates some aneuploidies that are well-tolerated and others that are highly lethal to the cell.…”