WRP Facilitates Filopodia Protrusion

Deformation of the plasma membrane—an early event in endocytosis and protrusion—is often produced by proteins containing BAR domains. These domains form curved structures that interact electrostatically with membrane lipids, causing the membrane to curve. Many such proteins also interact with proteins involved in regulation of actin polymerization, and thus they help to coordinate cytoskeletal and membrane dynamics. WAVE1-associated Racactivating protein (WRP) interacts with proteins that facilitate actin remodeling and has an inverse BAR domain, suggesting it causes membrane protrusion. Carlson et al. found that in cultured neurons, WRP was localized to dendritic filopodia and in buds along dendrites from which filopodia later emerged. Overexpression of WRP increased filopodia density, whereas knock-out reduced filopodia density in cultures and reduced the percentage of mature-looking spines in vivo. Loss of WRP impaired performance on several long-term memory tasks, which may explain why WRP mutation has been linked to mental retardation in humans.