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The Journal of Neuroscience, August 4, 2004, 24(31):6871-6879; doi:10.1523/JNEUROSCI.1538-04.2004

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Cellular/Molecular
Coordinating Structural and Functional Synapse Development: Postsynaptic p21-Activated Kinase Independently Specifies Glutamate Receptor Abundance and Postsynaptic Morphology

Stephanie D. Albin and Graeme W. Davis

Department of Biochemistry and Biophysics, Program in Neuroscience, University of California, San Francisco, San Francisco, California 94143

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.

Key words: GTPase; synaptic homeostasis; postsynaptic density; neurotransmitter receptor; synapse; Drosophila

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Received April 22, 2004; revised June 16, 2004; accepted June 17, 2004.

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