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EVL and MIM/MTSS1 Regulate Actin Cytoskeletal Remodeling to Promote Dendritic Filopodia in Neurons

Abstract

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.

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References
1.
Lohmann C, Bonhoeffer T . A role for local calcium signaling in rapid synaptic partner selection by dendritic filopodia. Neuron. 2008; 59(2):253-60. DOI: 10.1016/j.neuron.2008.05.025. View

2.
Bear J, Gertler F . Ena/VASP: towards resolving a pointed controversy at the barbed end. J Cell Sci. 2009; 122(Pt 12):1947-53. PMC: 2723151. DOI: 10.1242/jcs.038125. View

3.
Moffat J, Grueneberg D, Yang X, Kim S, Kloepfer A, Hinkle G . A lentiviral RNAi library for human and mouse genes applied to an arrayed viral high-content screen. Cell. 2006; 124(6):1283-98. DOI: 10.1016/j.cell.2006.01.040. View

4.
Spence E, Kanak D, Carlson B, Soderling S . The Arp2/3 Complex Is Essential for Distinct Stages of Spine Synapse Maturation, Including Synapse Unsilencing. J Neurosci. 2016; 36(37):9696-709. PMC: 5039249. DOI: 10.1523/JNEUROSCI.0876-16.2016. View

5.
Jourdain P, Fukunaga K, Muller D . Calcium/calmodulin-dependent protein kinase II contributes to activity-dependent filopodia growth and spine formation. J Neurosci. 2003; 23(33):10645-9. PMC: 6740921. View