Dictyostelium discoideum SecG interprets cAMP-mediated chemotactic signals to influence actin organization.

Tight control of actin cytoskeletal dynamics is essential for proper cell function and survival. Arf nucleotide binding-site opener (ARNO), a mammalian guanine nucleotide exchange factor for Arf, has been implicated in actin cytoskeletal regulation but its exact role is still unknown. To explore the role of ARNO in this regulation as well as in actin-mediated processes, the Dictyostelium discoideum homolog, SecG, was examined. SecG peaks during aggregation and mound formation. The overexpression of SecG arrests development at the mound stage. SecG overexpressing (SecG OE) cells fail to stream during aggregation. Although carA is expressed, SecG OE cells do not chemotax toward cAMP, indicating SecG is involved in the cellular response to cAMP. This chemotactic defect is specific to cAMP-directed chemotaxis, as SecG OE cells chemotax to folate without impairment and exhibit normal cell motility. The chemotactic defects of the SecG mutants may be due to an impaired cAMP response as evidenced by altered cell polarity and F-actin polymerization after cAMP stimulation. Cells overexpressing SecG have increased filopodia compared to wild type cells, implying that excess SecG causes abnormal organization of F-actin. The general function of the cytoskeleton, however, is not disrupted as the SecG OE cells exhibit proper cell-substrate adhesion. Taken together, the results suggest proper SecG levels are needed for appropriate response to cAMP signaling in order to coordinate F-actin organization during development.