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Volume 17, Number 1, Issue of January 1, 1997 pp. 152-159
Copyright ©1997 Society for NeuroscienceEssential Role for dlg in Synaptic Clustering of Shaker K+ Channels In Vivo
Received Sept. 4, 1996; revised Oct. 18, 1996; accepted Oct. 22, 1996.
Francisco J. Tejedor2, Amr Bokhari1, Oscar Rogero2, Michael Gorczyca1, Jiangwen Zhang1, Eunjoon Kim3, Morgan Sheng3, and Vivian Budnik1 1 Department of Biology, University of Massachusetts, Amherst, Massachusetts 01003, 2 Unidad Asociada-Consejo Superior de Investigaciones Científicas, Instituto de Neurociencias, Universidad de Alicante, San Juan 03080 Alicante, Spain, and 3 Howard Hughes Medical Institute, Massachusetts General Hospital, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02114
The assemblage of specific ion channels and receptors at synaptic sites is crucial for signaling between pre- and postsynaptic cells. However, the mechanisms by which proteins are targeted to and clustered at synapses are poorly understood. Here we show that the product of the Drosophila discs-large gene, DLG, is colocalized with Shaker K+ channels, which are clustered at glutamatergic synapses at the larval neuromuscular junction. In heterologous cells, DLG can cluster Shaker-type K+ channels, and, in the yeast two-hybrid system, the DLG PDZ1-2 domains bind directly to the C-terminal tail of Shaker proteins. We also demonstrate that DLG-Shaker interactions are required in vivo for Shaker clustering at the neuromuscular junction. Synaptic clustering of Shaker channels is abolished not only by mutations in dlg but also by a mutation in Shaker that deletes its C-terminal DLG binding motif. Analyses of various dlg mutant alleles suggest that channel clustering and synaptic targeting functions depend on distinct DLG domains. These studies demonstrate for the first time that DLG plays an important role in synaptic organization in vivo that correlates with its ability to bind directly to specific membrane proteins of the synapse.
Key words: discs-large; Drosophila; glutamatergic synapse; IA; ion channel clustering; MAGUK; neuromuscular junction; PDZ; potassium channels; PSD-95/SAP90; Shaker; synapse; synapse targeting
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