EVL and MIM/MTSS1 regulate actin cytoskeletal remodeling to promote dendritic filopodia in neurons

Dendritic spines are the postsynaptic compartment of a neuronal synapse and are critical for synaptic connectivity and plasticity. A developmental precursor to dendritic spines, dendritic filopodia (DF), facilitate synapse formation by sampling the environment for suitable axon partners during neurodevelopment and learning. Despite the significance of the actin cytoskeleton in driving these dynamic protrusions, the actin elongation factors involved are not well characterized. We identified the Ena/VASP protein EVL as uniquely required for the morphogenesis and dynamics of DF. Using a combination of genetic and optogenetic manipulations, we demonstrated that EVL promotes protrusive motility through membrane-direct actin polymerization at DF tips. EVL forms a complex at nascent protrusions and DF tips with MIM/MTSS1, an I-BAR protein important for the initiation of DF. We proposed a model in which EVL cooperates with MIM to coalesce and elongate branched actin filaments, establishing the dynamic lamellipodia-like architecture of DF. Parker et al. show that the Ena/VASP protein, EVL, complexes with the I-BAR protein, MIM/MTSS1, to drive filopodial protrusion from dendrites during neurodevelopment. These dendritic filopodia are precursors of dendritic spines and are critical for guiding neural connectivity. The findings presented here further our understanding of neural plasticity, which is compromised in several neurodevelopmental disorders.

Automated summary

Dendritic filopodia (DF) are precursors of dendritic spines and play a critical role in synaptic formation and neural connectivity. The study reveals that the Ena/VASP protein EVL complexes with the I-BAR protein MIM/MTSS1 to promote protrusion of DF. This finding enhances our understanding of neural plasticity and has implications for the treatment of neurodevelopmental disorders.