CYFIP/Sra-1 controls neuronal connectivity in Drosophila and links the Rac1 GTPase pathway to the fragile X protein.
Neuronal plasticity requires actin cytoskeleton remodeling and local protein translation in response to extracellular signals. Rho GTPase pathways control actin reorganization, while the fragile X mental retardation protein (FMRP) regulates the synthesis of specific proteins. Mutations affecting either pathway produce neuronal connectivity defects in model organisms and mental retardation in humans. We show that CYFIP, the fly ortholog of vertebrate FMRP interactors CYFIP1 and CYFIP2, is specifically expressed in the nervous system. CYFIP mutations affect axons and synapses, much like mutations in dFMR1 (the Drosophila FMR1 ortholog) and in Rho GTPase dRac1. CYFIP interacts biochemically and genetically with dFMR1 and dRac1. Finally, CYFIP acts as a dRac1 effector that antagonizes FMR1 function, providing a bridge between signal-dependent cytoskeleton remodeling and translation.
Schenck
Annette
A
Department of Molecular Pathology, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Boite Postale 10142, 67404 Illkirch, Cedex, France.
Bardoni
Barbara
B
Langmann
Caillin
C
Harden
Nicholas
N
Mandel
Jean Louis
JL
Giangrande
Angela
A
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001369:Axons / Q000502:physiology / Q000648:ultrastructure; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D003599:Cytoskeleton / Q000502:physiology / Q000648:ultrastructure; D004330:Drosophila / Q000254:growth & development / Q000502:physiology*; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology; D005123:Eye / Q000033:anatomy & histology / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1; D020558:GTP Phosphohydrolases / Q000378:metabolism; D017353:Gene Deletion; D015870:Gene Expression; D016296:Mutagenesis; D009154:Mutation; D009469:Neuromuscular Junction / Q000648:ultrastructure; D009473:Neuronal Plasticity; D009474:Neurons / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D013569:Synapses / Q000648:ultrastructure; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D020558:GTP Phosphohydrolases; D016601:RNA-Binding Proteins; D020744:rac GTP-Binding Proteins; C467328:FMR1 protein, Drosophila; C090146:Rac1 protein, Drosophila; C484666:Sra-1 protein, Drosophila