The exocyst complex binds the small GTPase RalA to mediate filopodia formation

Abstract
The Ras-related small GTPase RalA is involved in controlling actin cytoskeletal remodelling and vesicle transport in mammalian cells1,2. We identified the mammalian homologue of Sec5, a subunit of the exocyst complex determining yeast cell polarity, as a specific binding partner for GTP-ligated RalA. Inhibition of RalA binding to Sec5 prevents filopod production by tumor necrosis factor-α (TNF-α) and interleukin-1 (IL-1) and by activated forms of RalA and Cdc42, signalling intermediates downstream of these inflammatory cytokines. We propose that the RalA–exocyst complex interaction integrates the secretory and cytoskeletal pathways.