Building the cytokinetic ring: From molecular mechanisms to cellular function.

Abstract

Cytokinesis in animal and fungi is driven by a medial contractile ring of actin filaments and myosin motor proteins. The assembly and subsequent constriction of the ring requires coordination of the cellular patterning, cell cycle, actin cytoskeleton, and membrane trafficking systems. I will present recent progress in fission yeast where advanced genetics, microscopy, and biochemistry have enabled mathematical and computational models of the underlying biophysical mechanisms. A central role is played by “nodes,” large protein assemblies which form a medial band on the plasma membrane, condensing into a ring once actin filaments polymerized by node-bound formins are pulled by node-bound myosin. Nodes thus stabilize long range connections across the cell while also existing as a large structure in between nm and sub-μm scales. A characteristic of node proteins is their long intrinsically disordered regions (IDRs), heavily regulated by phosphorylation, including those of FBAR-containing Cdc15 and anillin-like Mid1. I will present computational modeling and experimental efforts by collaborators showing how phosphorylation promotes timely node assembly by tuning node IDR phase separation properties.