title: The functions of the actin nucleator Cobl in cellular morphogenesis critically depend on syndapin I.
abstract: 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.
authors: Institute for Biochemistry I, Jena University Hospital, Friedrich Schiller University Jena, Jena, Germany.
authors: Lukas
authors: L
authors: Schwintzer
authors: Nicole
authors: N
authors: Koch
authors: Rashmi
authors: R
authors: Ahuja
authors: Julia
authors: J
authors: Grimm
authors: Michael M
authors: MM
authors: Kessels
authors: Britta
authors: B
authors: Qualmann
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D006801:Humans; D047468:Immunoprecipitation; D051379:Mice; D008840:Microfilament Proteins; D018613:Microscopy, Confocal; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D011485:Protein Binding; D011506:Proteins / Q000378:metabolism*; D051381:Rats
chemical_list: D000199:Actins; D002352:Carrier Proteins; C096541:Cobl protein, mouse; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; C117738:Pacsin1 protein, rat; D011506:Proteins