title: Cordon-bleu is an actin nucleation factor and controls neuronal morphology.
abstract: Despite the wealth of different actin structures formed, only two actin nucleation factors are well established in vertebrates: the Arp2/3 complex and formins. Here, we describe a further nucleator, cordon-bleu (Cobl). Cobl is a brain-enriched protein using three Wiskott-Aldrich syndrome protein homology 2 (WH2) domains for actin binding. Cobl promotes nonbundled, unbranched filaments. Filament formation relies on barbed-end growth and requires all three Cobl WH2 domains and the extended linker L2. We suggest that the nucleation power of Cobl is based on the assembly of three actin monomers in cross-filament orientation. Cobl localizes to sites of high actin dynamics and modulates cell morphology. In neurons, induction of both neurites and neurite branching is dramatically increased by Cobl expression-effects that critically depend on Cobl's actin nucleation ability. Correspondingly, Cobl depletion results in decreased dendritic arborization. Thus, Cobl is an actin nucleator controlling neuronal morphology and development.
authors.affiliation: Department of Neurochemistry and Molecular Biology, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
authors.forename: Rashmi
authors.initials: R
authors.lastname: Ahuja
authors.forename: Roser
authors.initials: R
authors.lastname: Pinyol
authors.forename: Nicole
authors.initials: N
authors.lastname: Reichenbach
authors.forename: Laura
authors.initials: L
authors.lastname: Custer
authors.forename: John
authors.initials: J
authors.lastname: Klingensmith
authors.forename: Michael M
authors.initials: MM
authors.lastname: Kessels
authors.forename: Britta
authors.initials: B
authors.lastname: Qualmann
mesh_terms: D051376:Actin-Related Protein 2-3 Complex / Q000502:physiology; D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003598:Cytoskeletal Proteins; D006801:Humans; D051379:Mice; D008840:Microfilament Proteins; D008969:Molecular Sequence Data; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D010802:Phylogeny; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D051381:Rats
chemical_list: D051376:Actin-Related Protein 2-3 Complex; D000199:Actins; C096541:Cobl protein, mouse; D003598:Cytoskeletal Proteins; D008840:Microfilament Proteins; D011506:Proteins