Intramolecular regulation of anillin during cytokinesis

Abstract

Cytokinesis occurs by the ingression of an actomyosin ring that cleaves a cell into two daughters. This process is tightly controlled to avoid aneuploidy, and we previously showed that active Ran coordinates ring positioning with chromatin. Active Ran is high around chromatin, and forms an inverse gradient to cargo-bound importins. We found that the ring component anillin contains an NLS that binds to importin and is required for its function. Anillin contains a RhoA-binding domain (RBD), which we revealed autoinhibits the adjacent NLS-containing C2 domain. Here, we show that active RhoA relieves inhibition of the C2 domain. Furthermore, FRAP experiments show that the NLS regulates anillins cortical properties, supporting feedback to the RBD. Indeed, mutations that disrupt the interface between the RBD and C2 domain disrupt anillins localization and function. Thus, active RhoA induces a conformational change that increases accessibility to the C2 domain, which is maintained by importin-binding for recruitment to the equatorial cortex.