抄録
Ionotropic glutamate receptors (iGluRs) are preferentially expressed in dendrites and mediate excitatory synaptic transmission in the CNS. The mechanisms underlying such polarized sorting have recently begun to be characterized; dendrite-selective sorting often requires a short stretch of amino acids within the cytosolic domain of the membrane protein to be sorted. However, the molecules that recognize such sequence tags remain unknown in neurons. To understand the mechanism by which iGluRs are targeted to the somatodendritic domain, we determined the sequence tag mediating the polarized sorting within the C-terminus of the δ2 glutamate receptor (GluRδ2). We also identified a protein that specifically recognized this sequence tag. This protein, which we refer to as the dendrite targeting protein (DTP), was necessary and sufficient to steer GluRδ2 to the somatodendritic domain of hippocampal and cerebellar Purkinje neurons. Furthermore, DTP also associated with transmembrane AMPA receptor regulatory proteins (TARPs), which then controlled the polarized sorting of AMPA receptors in neurons. These results indicate that DTP-based vesicular trafficking system is one of the core mechanisms by which somatodendritic sorting of certain iGluRs is achieved. [J Physiol Sci. 2007;57 Suppl:S59]
