The N-terminal domain of Slack determines the formation and trafficking of Slick/Slack heteromeric sodium-activated potassium channels.
Potassium channels activated by intracellular Na(+) ions (K(Na)) play several distinct roles in regulating the firing patterns of neurons, and, at the single channel level, their properties are quite diverse. Two known genes, Slick and Slack, encode K(Na) channels. We have now found that Slick and Slack subunits coassemble to form heteromeric channels that differ from the homomers in their unitary conductance, kinetic behavior, subcellular localization, and response to activation of protein kinase C. Heteromer formation requires the N-terminal domain of Slack-B, one of the alternative splice variants of the Slack channel. This cytoplasmic N-terminal domain of Slack-B also facilitates the localization of heteromeric K(Na) channels to the plasma membrane. Immunocytochemical studies indicate that Slick and Slack-B subunits are coexpressed in many central neurons. Our findings provide a molecular explanation for some of the diversity in reported properties of neuronal K(Na) channels.
Chen
Haijun
H
Department of Biological Sciences, State University of New York at Albany, Albany, New York 12222, USA.
Kronengold
Jack
J
Yan
Yangyang
Y
Gazula
Valeswara-Rao
VR
Brown
Maile R
MR
Ma
Liqun
L
Ferreira
Gonzalo
G
Yang
Youshan
Y
Bhattacharjee
Arin
A
Sigworth
Fred J
FJ
Salkoff
Larry
L
Kaczmarek
Leonard K
LK
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D002460:Cell Line; D005260:Female; D006801:Humans; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D015221:Potassium Channels / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*; D000081033:Potassium Channels, Sodium-Activated; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000235:genetics / Q000502:physiology; D021381:Protein Transport / Q000235:genetics / Q000502:physiology; D051381:Rats; D014982:Xenopus laevis
C480493:Kcnt2 potassium channel, rat; D009419:Nerve Tissue Proteins; D015221:Potassium Channels; D000081033:Potassium Channels, Sodium-Activated; D020033:Protein Isoforms; C000626167:kcnt1 protein, rat