Abstract
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 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 syndapins. 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 in mammals.
Highlights
The actin cytoskeleton is crucial for a huge variety of key processes in cell biology
Cobl-like RNAi led to reduced Sholl intersections throughout the dendritic arbor (Figure 1—figure supplement 2H)
Development of proper dendritic arbors of neuronal cells is key for the complex brains of vertebrates, as neuronal morphologies have direct consequences for brain organization patterns, cell-cell connectivity, and information processing within neuronal networks
Summary
The actin cytoskeleton is crucial for a huge variety of key processes in cell biology. Only few factors were found that can promote the de novo formation of actin filaments (Chesarone and Goode, 2009; Qualmann and Kessels, 2009). The initial idea that each of the discovered actin nucleators may be responsible for the formation of specific, perhaps tissue- or cell-type-specific F-actin structures obviously had to be dismissed as too simple. The required functional diversity in actin filament formation despite a limited set of powerful effectors could be achieved by combinatory mechanisms specific for a given cell biological process. Experimental evidence for such combinatory actions of actin nucleators is still very sparse. On top of that, which mechanisms may orchestrate these powerful effectors to bring about a certain cellular processes remains a fundamental question in cell biology
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