RRC ID 21897
著者 Nahm M, Kim S, Paik SK, Lee M, Lee S, Lee ZH, Kim J, Lee D, Bae YC, Lee S.
タイトル dCIP4 (Drosophila Cdc42-interacting protein 4) restrains synaptic growth by inhibiting the secretion of the retrograde Glass bottom boat signal.
ジャーナル J Neurosci
Abstract The bone morphogenetic protein (BMP) ligand Glass bottom boat (Gbb) acts as a retrograde growth signal at the Drosophila neuromuscular junction (NMJ). Endocytic regulation of presynaptic BMP receptors has been proposed to attenuate retrograde BMP signaling. However, it remains unknown whether the Gbb signal is also regulated by postsynaptic mechanisms. Here, we provide evidence that Drosophila Cdc42-interacting protein 4 (dCIP4) functions postsynaptically to inhibit synaptic growth. dCIP4 is localized postsynaptically at NMJs. dcip4 mutations lead to synaptic overgrowth and increased presynaptic phosphorylated mothers against decapentaplegic (Mad) levels, and these defects are rescued by muscle-specific expression of dCIP4. Biochemical and genetic analyses demonstrate that dCIP4 acts downstream of Cdc42 to activate the postsynaptic Wsp-Arp2/3 pathway. We also show that BMP signaling is necessary for synaptic overgrowth in larvae lacking postsynaptic dcip4 or wsp. Finally, dCIP4 and Wsp inhibit Gbb secretion. Thus, we propose that dCIP4 restrains synaptic growth by inhibiting postsynaptic Gbb secretion through the Wsp-Arp2/3 pathway.
巻・号 30(24)
ページ 8138-50
公開日 2010-6-16
DOI 10.1523/JNEUROSCI.0256-10.2010
PII 30/24/8138
PMID 20554864
PMC PMC6634589
MeSH Analysis of Variance Animals Animals, Genetically Modified Bone Morphogenetic Proteins / genetics Bone Morphogenetic Proteins / metabolism Carrier Proteins / genetics Carrier Proteins / physiology* Cells, Cultured Drosophila Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila Proteins / physiology* Gene Expression Regulation, Developmental / physiology* Green Fluorescent Proteins / genetics Humans Microscopy, Confocal / methods Molecular Biology / methods Mutation / genetics Nerve Tissue Proteins / genetics Neuromuscular Junction / cytology Neuromuscular Junction / drug effects Neuromuscular Junction / physiology* Phosphorylation Presynaptic Terminals / metabolism RNA Interference / physiology Signal Transduction / genetics Transfection / methods Transforming Growth Factor beta / genetics Transforming Growth Factor beta / metabolism*
IF 5.674
引用数 29
WOS 分野 NEUROSCIENCES
リソース情報
ショウジョウバエ 15015R-2 15015R-3