dCIP4 (Drosophila Cdc42-interacting protein 4) restrains synaptic growth by inhibiting the secretion of the retrograde Glass bottom boat signal.
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.
Nahm
Minyeop
M
Interdisciplinary Graduate Program in Brain Science, Department of Cell and Developmental Biology, Dental Research Institute, Seoul National University, Seoul 110-740, Republic of Korea.
Kim
Sungdae
S
Paik
Sang Kyoo
SK
Lee
Mihye
M
Lee
Seongsoo
S
Lee
Zang Hee
ZH
Kim
Jaesang
J
Lee
Daekee
D
Bae
Yong Chul
YC
Lee
Seungbok
S
D000704:Analysis of Variance; D000818:Animals; D030801:Animals, Genetically Modified; D019485:Bone Morphogenetic Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002478:Cells, Cultured; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D018613:Microscopy, Confocal / Q000379:methods; D008967:Molecular Biology / Q000379:methods; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics; D009469:Neuromuscular Junction / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D010766:Phosphorylation; D017729:Presynaptic Terminals / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D015398:Signal Transduction / Q000235:genetics; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism*
D019485:Bone Morphogenetic Proteins; D002352:Carrier Proteins; C534739:Cip4 protein, Drosophila; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D016212:Transforming Growth Factor beta; C064196:dpp protein, Drosophila; C089440:gbb protein, Drosophila; D049452:Green Fluorescent Proteins