TY - JOUR
T1 - β Subunits promote K+ channel surface expression through effects early in biosynthesis
AU - Shi, Gongyi
AU - Nakahira, Kensuke
AU - Hammond, Scott
AU - Rhodes, Kenneth J.
AU - Schechter, Lee E.
AU - Trimmer, James
PY - 1996/4
Y1 - 1996/4
N2 - Voltage-gated K+ channels are protein complexes composed of ion- conducting integral membrane subunits and cytoplasmic β subunits. Here, we show that, in transfected mammalian cells, the predominant β subunit isoform in brain, Kvβ2, associates with the Kv1.2 α subunit early in channel biosynthesis and that Kvβ2 exerts multiple chaperone-like effects on associated Kv1.2 including promotion of cotranslational N-linked glycosylation of the nascent Kv1.2 polypeptide, increased stability of Kvβ2/Kv1.2 complexes, and increased efficiency of cell surface expression of Kv1.2. Taken together, these results indicate that while some cytoplasmic K+ channel β subunits affect the inactivation kinetics of α subunits, a more general, and perhaps more fundamental, role is to mediate the biosynthetic maturation and surface expression of voltage-gated K+ channel complexes. These findings provide a molecular basis for recent genetic studies indicating that β subunits are key determinants of neuronal excitability.
AB - Voltage-gated K+ channels are protein complexes composed of ion- conducting integral membrane subunits and cytoplasmic β subunits. Here, we show that, in transfected mammalian cells, the predominant β subunit isoform in brain, Kvβ2, associates with the Kv1.2 α subunit early in channel biosynthesis and that Kvβ2 exerts multiple chaperone-like effects on associated Kv1.2 including promotion of cotranslational N-linked glycosylation of the nascent Kv1.2 polypeptide, increased stability of Kvβ2/Kv1.2 complexes, and increased efficiency of cell surface expression of Kv1.2. Taken together, these results indicate that while some cytoplasmic K+ channel β subunits affect the inactivation kinetics of α subunits, a more general, and perhaps more fundamental, role is to mediate the biosynthetic maturation and surface expression of voltage-gated K+ channel complexes. These findings provide a molecular basis for recent genetic studies indicating that β subunits are key determinants of neuronal excitability.
UR - http://www.scopus.com/inward/record.url?scp=0029862913&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029862913&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(00)80104-X
DO - 10.1016/S0896-6273(00)80104-X
M3 - Article
C2 - 8608002
AN - SCOPUS:0029862913
VL - 16
SP - 843
EP - 852
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 4
ER -