Yu-Ting Mao and Matthew B. Dalva
Neural connections are initiated by motile dendritic and axonal protrusions, such as dendritic filopodia and axonal growth cones. Dendritic filopodia interview many axons and then choose the correct ones to make stable contacts. Specific rates of EphB activation in dendritic filopodia controls the decision of filopodia to reject or stabilize a synaptic contact onto an axon. However, it remains unknown how EphB activity in dendritic filopodia is modulated to regulate filopodial decisions. Here using an optogenetic approach, we find that photoactivation of a cis-interaction between EphB2 and ephrinB3 prevents filopodial retraction, likely driving filopodial stabilization. Using photoactivatable EphB2KD as a control, we show this effect is EphB2 kinase-dependent. In neurons, ephrinB3 is clustered in the tips of stable dendritic filopodia and localized on the cell surface. These data are consistent with the hypothesis that EphB activity controls filopodial movement and suggest a mechanism by which protein interaction may regulate the rate of kinase activity to drive distinctive cellular outcomes.
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