Ion channels and PSD-95 are colocalized in specific neuronal subcellular locations by an unknown mechanism. To investigate mechanisms of localization, we used biolistic techniques to express GFP-tagged PSD95 (PSD-95:GFP) and the K+-selective channel Kv1.4 in slices of rat cortex. In pyramidal cells, PSD- 95:GFP required a single PDZ domain and a region including the SH3 domain for localization to postsynaptic sites. When transfected alone, PSD-95:GFP was present in dendrites but absent from axons. When cotransfected with Kv1.4, PSD-95:GFP appeared in both axons and dendrites, while Kv1.4 was restricted to axons. When domains that mediate the interaction of Kv1.4 and PSD-95 were disrupted, Kv1.4 localized nonspecifically. Our results provide evidence that Kv1.4 itself may determine its subcellular location, while an associated MAGUK protein is a necessary but not sufficient co factor.
Arnold, D. B., & Clapham, D. E. (1999). Molecular determinants for subcellular localization of PSD-95 with an interacting K+ channel. Neuron, 23(1), 149–157. https://doi.org/10.1016/S0896-6273(00)80761-8