title: WAVE/SCAR, a multifunctional complex coordinating different aspects of neuronal connectivity.
abstract: Although it is well established that the WAVE/SCAR complex transduces Rac1 signaling to trigger Arp2/3-dependent actin nucleation, regulatory mechanisms of this complex and its versatile function in the nervous system are poorly understood. Here we show that the Drosophila proteins SCAR, CYFIP and Kette, orthologs of WAVE/SCAR complex components, all show strong accumulation in axons of the central nervous system and indeed form a complex in vivo. Neuronal defects of SCAR, CYFIP and Kette mutants are, despite the initially proposed function of CYFIP and Kette as SCAR silencers, indistinguishable and are as diverse as ectopic midline crossing and nerve branching as well as synapse undergrowth at the larval neuromuscular junction. The common phenotypes of the single mutants are readily explained by the finding that loss of any one of the three proteins leads to degradation of its partners. As a consequence, each mutant is unambiguously to be judged as defective in multiple components of the complex even though each component affects different signaling pathways. Indeed, SCAR-Arp2/3 signaling is known to control axonogenesis whereas CYFIP signaling to the Fragile X Mental Retardation Protein fly ortholog contributes to synapse morphology. Thus, our results identify the Drosophila WAVE/SCAR complex as a multifunctional unit orchestrating different pathways and aspects of neuronal connectivity.
authors.affiliation: Department of Developmental Biology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, B.P. 10142, 67404 Illkirch Cedex, C.U. de Strasbourg, France.
authors.forename: Annette
authors.initials: A
authors.lastname: Schenck
authors.forename: Abrar
authors.initials: A
authors.lastname: Qurashi
authors.forename: Pilar
authors.initials: P
authors.lastname: Carrera
authors.forename: Barbara
authors.initials: B
authors.lastname: Bardoni
authors.forename: Céline
authors.initials: C
authors.lastname: Diebold
authors.forename: Eyal
authors.initials: E
authors.lastname: Schejter
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mandel
authors.forename: Angela
authors.initials: A
authors.lastname: Giangrande
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002465:Cell Movement; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000196:embryology / Q000235:genetics; D051860:Fragile X Messenger Ribonucleoprotein 1; D005838:Genotype; D006801:Humans; D017403:In Situ Hybridization; D046911:Macromolecular Substances; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009469:Neuromuscular Junction / Q000033:anatomy & histology / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000378:metabolism*; D010641:Phenotype; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D051300:Wiskott-Aldrich Syndrome Protein Family
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D046911:Macromolecular Substances; D008840:Microfilament Proteins; D016601:RNA-Binding Proteins; D051300:Wiskott-Aldrich Syndrome Protein Family; C467328:FMR1 protein, Drosophila; C484666:Sra-1 protein, Drosophila; C478569:hem protein, Drosophila