engleski

Formins orchestrate the cortical actin cytoskeleton in amoeboid cell migration and large-scale endocytosis

Directed locomotion toward the food source and active internalization of nutrients represent defining traits of free-living single-celled eukaryotic organisms. Cells of the protist Dictyostelium discoideum represent a suitable model to study regulation of the actin cytoskeleton during amoeboid cell migration and large-scale endocytosis: phagocytosis and macropinocytosis. Dictyostelium cells are capable of translocating one cell length and recycling their fluid content in less than a minute, using the basic constituents and regulatory mechanisms common to the actin cytoskeleton of all eukaryotes. For example, actin polymerases from the formin family nucleate and elongate linear actin filaments and, together with the Arp2/3 complex, represent the major promoters of actin assembly in Dictyostelium. In the first part of the talk, I will present the main mechanism of de novo generation of actin filaments at the back of polarized cells mediated by Diaphanous- related formin A (ForA). Further stabilization of the posterior actin cortex is accomplished by actin crosslinkers and IQGAP-related proteins, and their localization and activity is regulated by small GTPases and phosphoinositide lipids. Next, I will show how the activity of another Diaphanous-related formin from Dictyostelium, formin G (ForG), underlies actin assembly in large-scale endocytosis. ForG localizes to endocytic cups, efficiently elongates actin filaments in the presence of profilin, and the diminished actin content in the cups of ForG-null mutants is associated with a strongly impaired endocytosis. Interestingly, ForG is directly regulated in large-scale endocytosis by small GTPases RasB and RasG, which are highly related to the human proto-oncogene KRas. Taken together, the presented data will illustrate highly diversified functional roles that structurally similar proteins from the formin family play in the regulation of actin-driven processes.

formins ; Dictyostelium ; cell migration ; large-scale endocytosis ; Ras

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