Clustering of neuronal potassium channels is independent of their interaction with PSD-95.
Voltage-dependent potassium channels regulate membrane excitability and cell-cell communication in the mammalian nervous system, and are found highly localized at distinct neuronal subcellular sites. Kv1 (mammalian Shaker family) potassium channels and the neurexin Caspr2, both of which contain COOH-terminal PDZ domain binding peptide motifs, are found colocalized at high density at juxtaparanodes flanking nodes of Ranvier of myelinated axons. The PDZ domain-containing protein PSD-95, which clusters Kv1 potassium channels in heterologous cells, has been proposed to play a major role in potassium channel clustering in mammalian neurons. Here, we show that PSD-95 colocalizes precisely with Kv1 potassium channels and Caspr2 at juxtaparanodes, and that a macromolecular complex of Kv1 channels and PSD-95 can be immunopurified from mammalian brain and spinal cord. Surprisingly, we find that the high density clustering of Kv1 channels and Caspr2 at juxtaparanodes is normal in a mutant mouse lacking juxtaparanodal PSD-95, and that the indirect interaction between Kv1 channels and Caspr2 is maintained in these mutant mice. These data suggest that the primary function of PSD-95 at juxtaparanodes lies outside of its accepted role in mediating the high density clustering of Kv1 potassium channels at these sites.
Rasband
Matthew N
MN
Department of Biochemistry and Cell Biology, State University of New York at Stony Brook, Stony Brook, NY 11794, USA.
Park
Eunice W
EW
Zhen
Dongkai
D
Arbuckle
Margaret I
MI
Poliak
Sebastian
S
Peles
Elior
E
Grant
Seth G N
SG
Trimmer
James S
JS
D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D019556:COS Cells; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D051663:Kv1.2 Potassium Channel; D046911:Macromolecular Substances; D008565:Membrane Proteins; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011485:Protein Binding; D051381:Rats
D000911:Antibodies, Monoclonal; C403049:CNTNAP2 protein, human; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C496970:Kcna2 protein, mouse; C496972:Kcna2 protein, rat; D051663:Kv1.2 Potassium Channel; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; C033652:postsynaptic density proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases