SIP-2/FIP modulates PRC-1/FEO to ensure proper cytokinesis and ploidy

Authors

• RK Ng
• ZT Swider
• R Varadarajan
• NM Rusan

Abstract

Mitosis is a fundamental process required for cell proliferation and development. The final stages of mitosis include the segregation of the duplicated genome in anaphase and the physical separation of daughter cells by cytokinesis. Defects in either of these late mitotic stages have profound implications for human health such as tumorigenesis and birth defects associated with aneuploidy. Both chromosome segregation and cytokinesis rely, in part, on intricate microtubule (MT)-based structures, which are organized by MT associated proteins (MAPs), molecular motors, and other regulatory elements. One critical MAP, Fascetto (FEO), crosslinks MTs in anaphase to form the central spindle and localizes key proteins such as the Chromosomal Passenger Complex for anaphase progression. FEO localization at the cytokinetic furrow in telophase also recruits midbody proteins necessary for proper cell abscission. We identified Septin-interacting protein (SIP-2) as a novel FEO binding partner and have renamed SIP-2 to FIP (FEO interacting protein). We used Y2H analysis to show that the FEO-FIP interaction is direct and also live cell imaging and co-immunoprecipitation experiments to show that the interaction occurs in mitosis. Loss of function analysis showed that FIP is necessary for proper chromosome segregation, mitotic progression, and both MT and midbody stability. Finally, loss of either FEO or FIP led to failed cytokinesis and polyploidy, ultimately leading to tumor-like masses in the brain. Thus, we have identified a novel mechanism that relies on the FEO-FIP interaction for regulation of late-stage cell division.

Scientific Focus Area: Cell Biology

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