The Ras1-mitogen-activated protein kinase signal transduction pathway regulates synaptic plasticity through fasciclin II-mediated cell adhesion.
Ras proteins are small GTPases with well known functions in cell proliferation and differentiation. In these processes, they play key roles as molecular switches that can trigger distinct signal transduction pathways, such as the mitogen-activated protein kinase (MAPK) pathway, the phosphoinositide-3 kinase pathway, and the Ral-guanine nucleotide dissociation stimulator pathway. Several studies have implicated Ras proteins in the development and function of synapses, but the molecular mechanisms for this regulation are poorly understood. Here, we demonstrate that the Ras-MAPK pathway is involved in synaptic plasticity at the Drosophila larval neuromuscular junction. Both Ras1 and MAPK are expressed at the neuromuscular junction, and modification of their activity levels results in an altered number of synaptic boutons. Gain- or loss-of-function mutations in Ras1 and MAPK reveal that regulation of synapse structure by this signal transduction pathway is dependent on fasciclin II localization at synaptic boutons. These results provide evidence for a Ras-dependent signaling cascade that regulates fasciclin II-mediated cell adhesion at synaptic terminals during synapse growth.
Koh
Young-Ho
YH
Department of Biology, Neuroscience and Behavior Program, University of Massachusetts, Amherst, Massachusetts 01003, USA.
Ruiz-Canada
Catalina
C
Gorczyca
Michael
M
Budnik
Vivian
V
D000818:Animals; D002448:Cell Adhesion / Q000502:physiology; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila; D029721:Drosophila Proteins; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007814:Larva; D020935:MAP Kinase Signaling System / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009469:Neuromuscular Junction / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology*; D018631:ras Proteins
D015816:Cell Adhesion Molecules, Neuronal; D029721:Drosophila Proteins; C051642:fasciclin II; D020928:Mitogen-Activated Protein Kinases; D019204:GTP-Binding Proteins; C417283:Ras85D protein, Drosophila; D018631:ras Proteins