Vavylonis D. Model of For3p-mediated actin cable assembly in fission yeast

Formin For3p nucleates actin cables at the tips of fission yeast cells for polarized cell growth. The results of prior experiments have suggested a possible mechanism for actin cable assembly that involves association of For3p near cell tips, For3p-mediated actin polymerization, retrograde flow of actin cables toward the cell center, For3p dissociation from cell tips, and cable disassembly. We used analytical and computational modeling to test the validity and implications of the proposed coupled For3p/actin mechanism. We compared the model to prior experiments quantitatively and generated predictions for the expected behavior of the actin cable system upon changes of parameter values. We found that the model generates stable steady states with realistic values of rate constants and actin and For3p concentrations. Comparison of our results to previous experiments monitoring the FRAP of For3p-3GFP and the response of actin cables to treatments with actin depolymerizing drugs provided further support for the model. We identified the set of parameter values that produces results in agreement with experimental observations. We discuss future experiments that will help test the model’s predictions and eliminate other possible mechanisms. The results of the model suggest that flow of actin cables may establish actin and For3p concentration gradients in the cytoplasm that could be important in global cell patterning