Coordinating structural and functional synapse development: postsynaptic p21-activated kinase independently specifies glutamate receptor abundance and postsynaptic morphology.
Here, we show that postsynaptic p21-activated kinase (Pak) signaling diverges into two genetically separable pathways at the Drosophila neuromuscular junction. One pathway controls glutamate receptor abundance. Pak signaling within this pathway is specified by a required interaction with the adaptor protein Dreadlocks (Dock). We demonstrate that Dock is localized to the synapse via an Src homology 2-mediated protein interaction. Dock is not necessary for Pak localization but is necessary to restrict Pak signaling to control glutamate receptor abundance. A second genetically separable function of Pak kinase signaling controls muscle membrane specialization through the regulation of synaptic Discs-large. In this pathway, Dock is dispensable. We present a model in which divergent Pak signaling is able to coordinate two different features of postsynaptic maturation, receptor abundance, and muscle membrane specialization.
Albin
Stephanie D
SD
Department of Biochemistry and Biophysics, Program in Neuroscience, University of California, San Francisco, San Francisco, California 94143, USA.
Davis
Graeme W
GW
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000502:physiology*; D020558:GTP Phosphohydrolases / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000502:physiology; D009469:Neuromuscular Junction / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D017470:Receptors, Glutamate / Q000502:physiology*; D013569:Synapses / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000502:physiology; D054462:p21-Activated Kinases
D048868:Adaptor Proteins, Signal Transducing; D029721:Drosophila Proteins; D009419:Nerve Tissue Proteins; D017470:Receptors, Glutamate; D025521:Tumor Suppressor Proteins; C099753:dock protein, Drosophila; C070350:dlg1 protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D054462:p21-Activated Kinases; D020558:GTP Phosphohydrolases