Journal Article

The functions of the actin nucleator Cobl in cellular morphogenesis critically depend on syndapin I

Ahuja, Rashmi, Grimm, Julia, Koch, Nicole, Kessels, Michael M, Qualmann, Britta, Schwintzer, Lukas

2011

Overview

Spatial control of cortical actin nucleation is indispensable for proper establishment and plasticity of cell morphology. Cobl is a novel WH2 domain‐based actin nucleator. The cellular coordination of Cobl's nucleation activity, however, has remained elusive. Here, we reveal that Cobl's cellular functions are dependent on syndapin. Cobl/syndapin complexes form in vivo , as demonstrated by colocalization, coimmunoprecipitation and subcellular recruitment studies. In vitro reconstitutions and subcellular fractionations demonstrate that, via its lipid‐binding Fer/CIP4 Homology (FCH)‐Bin/Amphiphysin/Rvs (F‐BAR) domain, syndapin recruits Cobl to membranes. Consistently, syndapin I RNAi impairs cortical localization of Cobl. Further functional studies in neurons show that Cobl and syndapin I work together in dendritic arbor development. Importantly, both proteins are crucial for dendritogenesis. Cobl‐mediated functions in neuromorphogenesis critically rely on syndapin I and interestingly also on Arp3. Endogenous Cobl, syndapin I and the Arp2/3 complex activator and syndapin‐binding partner N‐WASP were present in one complex, as demonstrated by coimmunoprecipitations. Together, these data provide detailed insights into the molecular basis for Cobl‐mediated functions and reveal that different actin nucleators are functionally intertwined by syndapin I during neuromorphogenesis. Here, an interaction between the actin nucleator Cobl and the F‐BAR domain protein Syndapin is shown to recruit Cobl to the membrane, where it regulates the actin cytoskeleton during neuronal dendritogenesis.

• Publisher: John Wiley & Sons, Ltd,Nature Publishing Group UK,Springer Nature B.V,Nature Publishing Group
• Subject: Actins - metabolism / Animals / Binding sites / Carrier Proteins - metabolism / cell cortex / Cell Line / Cell Membrane - metabolism / Cell morphology / cordon-bleu / cytoskeleton / Humans / Immunoprecipitation / Mice / Microscopy, Confocal / Molecular biology / Morphology / N-WASP and Arp2/3 complex-mediated actin nucleation / neuronal cell morphology / Neurons - cytology / Neurons - metabolism / Nucleation / Plasticity / Protein Binding / Proteins / Proteins - metabolism / Rats