Length Regulation of Actin Filament Arrays

Abstract

The cytoskeleton controls the movements of cellular substructures and governs dynamic changes in the cell shape. A key question in cell biology is how cytoskeletal structures are established and maintained. We use a combination of experiment and theory to develop quantitative models for describing the regulation of the actin cytoskeleton size and shape. In particular, we focus on actin cables in budding yeast cells, structures which are used for intracellular transport that is essential for polarized cell growth. In yeast, actin cables grow to span the entire length of the mother cell compartment and contour its curved surface. The regulation of cable length is essential because overgrowth of the cables causes misdirection of intracellular transport.Experiments suggest that key physical parameters in actin cable formation, such as the rates of assembly and disassembly of the actin polymers are controlled by specific actin-binding proteins. There is substantial amount of information about these individual proteins, but how their functions are integrated to produce the desired cable morphology is not well understood. Among the key proteins are formins, which catalyze both the nucleation and elongation of actin filaments. A recent experiment showed that another protein Smy1 binds to formins to decrease the actin elongation rate and that this interaction is critical for maintaining proper actin cable length and shape. Further, it was shown that the Smy1 proteins are transported by myosinV on cables to the bud neck, where the formins are anchored, suggesting a feedback mechanism that makes assembly rate length-dependent. Incorporating this mechanism, we compute the probability distribution of cable lengths as a function of parameters such as Smy1 binding strength and speed of myosin motors that deliver it to the formin. These results provide experimentally testable predictions of our proposed model of cable length control.