Membrane protein condensates polymerize actin and form filopodia

Filopodia are slender, finger-like plasma membrane protrusions. In neuronal cells, filopodia mature into specialized compartments including neurites, axon branches and synapses. Consequently, filopodia are important for the formation of neuronal circuits during brain development. Primarily composed of parallel bundles of actin filaments, filopodia formation, stabilization and dynamics are regulated by various proteins that associate with both actin filaments and the plasma membrane. Consequently, a precise actin-membrane communication underlies the process of filopodia formation during neuronal growth and morphogenesis.

Among the membrane proteins implicated in filopodia formation, Phospholipid Phosphatase-Related Protein 3 (PLPPR3) has emerged as important regulator of this process in neurons. PLPPR3 is composed of six transmembrane domains and a long disordered intracellular domain (ICD). I would like to discuss our new work, which shows that the intracellular domain of PLPPR3 forms liquid condensates both in cells and in vitro. These condensates induces strong co-partitioning of actin monomers into condensates, promoting actin nucleation and polymerization. Our findings suggest a biophysical mechanism by which PLPPR3 regulates actin cytoskeleton remodeling at plasma membranes, providing insights into how phase separation can drive neuronal morphogenesis and growth.