PKCε associates with the Kv3.4 channel to promote its expression in a kinase activity-dependent manner.
Kv3.4
PKCε
dorsal root ganglia
Journal
FASEB journal : official publication of the Federation of American Societies for Experimental Biology
ISSN: 1530-6860
Titre abrégé: FASEB J
Pays: United States
ID NLM: 8804484
Informations de publication
Date de publication:
01 2021
01 2021
Historique:
received:
24
07
2019
revised:
05
11
2020
accepted:
19
11
2020
entrez:
28
12
2020
pubmed:
29
12
2020
medline:
16
6
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33368632
doi: 10.1096/fj.201901877R
doi:
Substances chimiques
KCNC4 protein, human
0
Kcnc4 protein, rat
0
Shaw Potassium Channels
0
Prkce protein, rat
EC 2.7.1.-
PRKCE protein, human
EC 2.7.11.13
Protein Kinase C-epsilon
EC 2.7.11.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e21241Subventions
Organisme : NINDS NIH HHS
ID : F31 NS090689
Pays : United States
Organisme : NIH HHS
ID : NS079855
Pays : United States
Organisme : NIH HHS
ID : NS090689
Pays : United States
Informations de copyright
© 2020 Federation of American Societies for Experimental Biology.
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