A role for Kif17 in transport of Kv4.2.
Although kinesins are known to transport neuronal proteins, it is not known what role they play in the targeting of their cargos to specific subcellular compartments in neurons. Here we present evidence that the K+ channel Kv4.2, which is a major regulator of dendritic excitability, is transported to dendrites by the kinesin isoform Kif17. We show that a dominant negative construct against Kif17 dramatically inhibits localization to dendrites of both introduced and endogenous Kv4.2, but those against other kinesins found in dendrites do not. Kv4.2 colocalizes with Kif17 but not with other kinesin isoforms in dendrites of cortical neurons. Native Kv4.2 and Kif17 coimmunoprecipitate from brain lysate, and introduced, tagged versions of the two proteins coimmunoprecipitate from COS cell lysate, indicating that the two proteins interact, either directly or indirectly. The interaction between Kif17 and Kv4.2 appears to occur through the extreme C terminus of Kv4.2 and not through the dileucine motif. Thus, the dileucine motif does not determine the localization of Kv4.2 by causing the channel to interact with a specific motor protein. In support of this conclusion, we found that the dileucine motif mediates dendritic targeting of CD8 independent of Kif17. Together our data show that Kif17 is probably the motor that transports Kv4.2 to dendrites but suggest that this motor does not, by itself, specify dendritic localization of the channel.
Chu
Po-Ju
PJ
Department of Biology and Program in Molecular and Computational Biology, University of Southern California, Los Angeles, California 90089-2910, USA.
Rivera
Jacqueline F
JF
Arnold
Don B
DB
D000818:Animals; D001692:Biological Transport / Q000502:physiology; D019556:COS Cells; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000378:metabolism*; D005260:Female; D016547:Kinesins / Q000235:genetics / Q000378:metabolism*; D007930:Leucine / Q000378:metabolism; D051379:Mice; D008815:Mice, Inbred Strains; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism / Q000648:ultrastructure; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
C409642:KIF17 protein, mouse; D020409:Molecular Motor Proteins; D051672:Shal Potassium Channels; D016547:Kinesins; D007930:Leucine