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PKCε associates with the Kv3.4 channel to promote its expression in a kinase activity‐dependent manner
Author(s) -
Zemel Benjamin M.,
Zhi Lianteng,
Brown Eric V.,
Tymanskyj Stephen R.,
Liang Qiansheng,
Covarrubias Manuel
Publication year - 2021
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901877r
Subject(s) - dorsal root ganglion , protein kinase c , microbiology and biotechnology , gating , chemistry , heterologous expression , potassium channel , signal transduction , neuroscience , biology , spinal cord , biochemistry , endocrinology , gene , recombinant dna
The voltage‐gated potassium channel Kv3.4 is a crucial regulator of nociceptive signaling in the dorsal root ganglion (DRG) and the dorsal horn of the spinal cord. Moreover, Kv3.4 dysfunction has been linked to neuropathic pain. Although kinases and phosphatases can directly modulate Kv3.4 gating, the signaling mechanisms regulating the expression and stability of the Kv3.4 protein are generally unknown. We explored a potential role of PKCε and found an unexpected interaction that has a positive effect on Kv3.4 expression. Co‐immunoprecipitation studies revealed a physical association between PKCε and Kv3.4 in both heterologous cells and rat DRG neurons. Furthermore, in contrast to the wild‐type and constitutively active forms of PKCε, expression of a catalytically inactive form of the enzyme inhibits Kv3.4 expression and membrane localization through a dominant negative effect. Co‐expression of Kv3.4 with the wild‐type, constitutively active, or catalytically inactive forms of PKCε had no significant effects on Kv3.4 gating. These results suggest that a novel physical interaction of the Kv3.4 channel with functional PKCε primarily determines its stability and localization in DRG neurons. This interaction is akin to those of previously identified accessory ion channel proteins, which could be significant in neural tissues where Kv3.4 regulates electrical signaling.