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The functions of the actin nucleator Cobl in cellular morphogenesis critically depend on syndapin I
Author(s) -
Schwintzer Lukas,
Koch Nicole,
Ahuja Rashmi,
Grimm Julia,
Kessels Michael M,
Qualmann Britta
Publication year - 2011
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/emboj.2011.207
Subject(s) - biology , morphogenesis , actin , microbiology and biotechnology , genetics , gene
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.