Surface expression of Kv1 channels is governed by a C-terminal motif.
Voltage-gated K(+) channel subunits must reach the plasma membrane to repolarize action potentials. Yet the efficiency of cell surface targeting varies among Kv subunits with some requiring auxiliary subunits for optimal expression. Here we identify a conserved motif located in the variable C-terminal region of Kv1 channels that controls the efficiency of functional channel expression. Variations among wild type channels in the optimal sequence VXXSL produce differences in distribution and the requirement for auxiliary subunits. Furthermore, deletion of this motif decreases subunit glycosylation and surface localization but does not prohibit subunit multimerization. Finally, the action of the essential sequence is shown to be independent of the chaperone effect of Kvbeta subunits. Thus, the newly identified C-terminal motif governs processing and cell surface expression of Kv1 voltage-gated K(+) channels.
Li
D
D
Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Takimoto
K
K
Levitan
E S
ES
D000200:Action Potentials; D000595:Amino Acid Sequence; D002460:Cell Line; D017124:Conserved Sequence; D004591:Electrophoresis, Polyacrylamide Gel; D005786:Gene Expression Regulation; D006031:Glycosylation; D049452:Green Fluorescent Proteins; D006801:Humans; D007202:Indicators and Reagents; D051663:Kv1.2 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008164:Luminescent Proteins; D008969:Molecular Sequence Data; D015221:Potassium Channels / Q000096:biosynthesis* / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011487:Protein Conformation; D017384:Sequence Deletion; D013329:Structure-Activity Relationship; D013499:Surface Properties
D007202:Indicators and Reagents; C496969:KCNA2 protein, human; C496977:KCNA4 protein, human; C496981:KCNA5 protein, human; D051663:Kv1.2 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008164:Luminescent Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D049452:Green Fluorescent Proteins