The Cdc42-selective GAP rich regulates postsynaptic development and retrograde BMP transsynaptic signaling.
Retrograde bone morphogenetic protein signaling mediated by the Glass bottom boat (Gbb) ligand modulates structural and functional synaptogenesis at the Drosophila melanogaster neuromuscular junction. However, the molecular mechanisms regulating postsynaptic Gbb release are poorly understood. In this study, we show that Drosophila Rich (dRich), a conserved Cdc42-selective guanosine triphosphatase-activating protein (GAP), inhibits the Cdc42-Wsp pathway to stimulate postsynaptic Gbb release. Loss of dRich causes synaptic undergrowth and strongly impairs neurotransmitter release. These presynaptic defects are rescued by targeted postsynaptic expression of wild-type dRich but not a GAP-deficient mutant. dRich inhibits the postsynaptic localization of the Cdc42 effector Wsp (Drosophila orthologue of mammalian Wiskott-Aldrich syndrome protein, WASp), and manifestation of synaptogenesis defects in drich mutants requires Wsp signaling. In addition, dRich regulates postsynaptic organization independently of Cdc42. Importantly, dRich increases Gbb release and elevates presynaptic phosphorylated Mad levels. We propose that dRich coordinates the Gbb-dependent modulation of synaptic growth and function with postsynaptic development.
Interdisplinary Program in Brain Science, Seoul National University, Seoul, Republic of Korea.
Minyeop
M
Nahm
A Ashleigh
AA
Long
Sang Kyoo
SK
Paik
Sungdae
S
Kim
Yong Chul
YC
Bae
Kendal
K
Broadie
Seungbok
S
Lee
D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism* / Q000502:physiology; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000378:metabolism*; D020690:GTPase-Activating Proteins / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000378:metabolism* / Q000502:physiology; D051316:Wiskott-Aldrich Syndrome Protein / Q000502:physiology; D020764:cdc42 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
D019485:Bone Morphogenetic Proteins; D029721:Drosophila Proteins; D020690:GTPase-Activating Proteins; D016212:Transforming Growth Factor beta; C477859:WASp protein, Drosophila; D051316:Wiskott-Aldrich Syndrome Protein; C089440:gbb protein, Drosophila; D020764:cdc42 GTP-Binding Protein