PT - JOURNAL ARTICLE AU - Maryam Izadi AU - Eric Seemann AU - Dirk Schlobinski AU - Lukas Schwintzer AU - Britta Qualmann AU - Michael M. Kessels TI - Functional interdependence of the actin nucleator Cobl and Cobl-like in dendritic arbor development AID - 10.1101/2021.03.03.433715 DP - 2021 Jan 01 TA - bioRxiv PG - 2021.03.03.433715 4099 - http://biorxiv.org/content/early/2021/03/03/2021.03.03.433715.short 4100 - http://biorxiv.org/content/early/2021/03/03/2021.03.03.433715.full AB - Local actin filament formation is indispensable for development of the dendritic arbor of neurons. We show that, surprisingly, the action of single actin filament-promoting factors was insufficient for powering dendritogenesis. Instead, this process required the actin nucleator Cobl and its only evolutionary distant ancestor Cobl-like acting interdependently. This coordination between Cobl-like and Cobl was achieved by physical linkage by syndapin I. Syndapin I formed nanodomains at convex plasma membrane areas at the base of protrusive structures and interacted with three motifs in Cobl-like, one of which was Ca2+/calmodulin-regulated. Consistently, syndapin I, Cobl-like’s newly identified N terminal calmodulin-binding site and the single Ca2+/calmodulin-responsive syndapin-binding motif all were critical for Cobl-like’s functions. In dendritic arbor development, local Ca2+/CaM-controlled actin dynamics thus relies on regulated and physically coordinated interactions of different F-actin formation-promoting factors and only together they have the power to bring about the sophisticated neuronal morphologies required for neuronal network formation.