RGD Reference Report - The functions of the actin nucleator Cobl in cellular morphogenesis critically depend on syndapin I. - Rat Genome Database

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

Authors: Schwintzer, L  Koch, N  Ahuja, R  Grimm, J  Kessels, MM  Qualmann, B 
Citation: Schwintzer L, etal., EMBO J. 2011 Jul 1;30(15):3147-59. doi: 10.1038/emboj.2011.207.
RGD ID: 8554579
Pubmed: PMID:21725280   (View Abstract at PubMed)
PMCID: PMC3160182   (View Article at PubMed Central)
DOI: DOI:10.1038/emboj.2011.207   (Journal Full-text)

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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of dendrite development involved_inIDA 8554579PMID:21725280BHF-UCL 
protein localization to plasma membrane involved_inIDA 8554579PMID:21725280BHF-UCL 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cell cortex located_inIDA 8554579PMID:21725280BHF-UCL 
perinuclear region of cytoplasm located_inIDA 8554579PMID:21725280BHF-UCL 
plasma membrane located_inIDA 8554579; 8554579PMID:21725280BHF-UCL 
synapse located_inIDA 8554579PMID:21725280BHF-UCL 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q9Z0W58554579PMID:21725280IntAct 
protein binding enablesIPIUniProtKB:D3ZUI58554579PMID:21725280IntAct 
protein binding enablesIPIUniProtKB:Q5NBX18554579; 8554579PMID:21725280BHF-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Cobl  (cordon-bleu WH2 repeat protein)
Pacsin1  (protein kinase C and casein kinase substrate in neurons 1)
Pacsin2  (protein kinase C and casein kinase substrate in neurons 2)


Additional Information