PAR-1 kinase phosphorylates Dlg and regulates its postsynaptic targeting at the Drosophila neuromuscular junction.
Targeting of synaptic molecules to their proper location is essential for synaptic differentiation and plasticity. PSD-95/Dlg proteins have been established as key components of the postsynapse. However, the molecular mechanisms regulating the synaptic targeting, assembly, and disassembly of PSD-95/Dlg are not well understood. Here we show that PAR-1 kinase, a conserved cell polarity regulator, is critically involved in controlling the postsynaptic localization of Dlg. PAR-1 is prominently localized at the Drosophila neuromuscular junction (NMJ). Loss of PAR-1 function leads to increased synapse formation and synaptic transmission, whereas overexpression of PAR-1 has the opposite effects. PAR-1 directly phosphorylates Dlg at a conserved site and negatively regulates its mobility and targeting to the postsynapse. The ability of a nonphosphorylatable Dlg to largely rescue PAR-1-induced synaptic defects supports the idea that Dlg is a major synaptic substrate of PAR-1. Control of Dlg synaptic targeting by PAR-1-mediated phosphorylation thus constitutes a critical event in synaptogenesis.
Zhang
Yali
Y
Department of Pathology, Stanford University School of Medicine, GRECC/VAPAHCS, Palo Alto, CA 94304, USA.
Guo
Huifu
H
Kwan
Helen
H
Wang
Ji-Wu
JW
Kosek
Jon
J
Lu
Bingwei
B
D000818:Animals; D030801:Animals, Genetically Modified; D004330:Drosophila / Q000502:physiology*; D029721:Drosophila Proteins / Q000378:metabolism* / Q000502:physiology*; D036681:Fluorescence Recovery After Photobleaching; D038362:Glycogen Synthase Kinase 3; D066298:In Vitro Techniques; D009469:Neuromuscular Junction / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D014018:Tissue Distribution; D025521:Tumor Suppressor Proteins / Q000378:metabolism*
D029721:Drosophila Proteins; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; D038362:Glycogen Synthase Kinase 3; C472496:Par-1 protein, Drosophila