Membrane protein condensates polymerize actin and form filopodia

Neuronal morphogenesis is guided by filopodia, dynamically generated plasma membrane protrusions filled with parallel actin filaments. However, how filopodial actin filaments are locally produced, organized, and maintained remains unclear. The transmembrane protein PLPPR3 induces filopodia in neurons and other cells. We find that the intracellular domain (ICD) of PLPPR3 forms liquid condensates, which exhibit strong co-partitioning of actin monomers. These condensates promote actin polymerization within the condensates at the expense of actin monomers in the environment, consistent with thermodynamic coupling of actin partitioning and polymerization, which we recapitulate in a modified polymerization kinetics model. This mechanism requires favorable actin partitioning into the condensate relative to the environment. Using crosslinking mass spectrometry, we identify a WH2-like actin-affinity domain within the PLPPR3 ICD. Deleting this domain lowers actin partitioning in vitro and decreases filopodia formation in vivo. Our findings establish a previously unrecognized mechanism for actin network remodeling, in which condensates act as actin sinks, locally boosting monomer concentrations and facilitating polymerization of actin filaments.