RT Journal Article
SR Electronic
T1 Essential Role for <em>dlg</em> in Synaptic Clustering of Shaker K<sup>+</sup> Channels <em>In Vivo</em>
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 152
OP 159
DO 10.1523/JNEUROSCI.17-01-00152.1997
VO 17
IS 1
A1 Tejedor, Francisco J.
A1 Bokhari, Amr
A1 Rogero, Oscar
A1 Gorczyca, Michael
A1 Zhang, Jiangwen
A1 Kim, Eunjoon
A1 Sheng, Morgan
A1 Budnik, Vivian
YR 1997
UL http://www.jneurosci.org/content/17/1/152.abstract
AB 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 theDrosophila 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.