The Kv1.2 potassium channel: the position of an N-glycan on the extracellular linkers affects its protein expression and function.
Voltage-gated potassium Kv1 channels have three extracellular linkers, the S1-S2, the S3-S4, and the S5-P. The S1-S2 is the only linker that has an N-glycan and it is at a conserved position on this linker on Kv1.1-Kv1.5 and Kv1.7 channels. We hypothesize that an N-glycan is found at only this position due to its effect on folding, trafficking, and/or function of these channels. To investigate this hypothesis, N-glycosylation sites were engineered at different positions on the extracellular linkers of Kv1.2 to determine the effects of N-glycans on channel surface protein expression and function. Our data suggest that for Kv1 channels, (1) placing an N-glycan at non-native positions on the S1-S2 linker decreased cell surface protein expression but the N-glycan still affected function similarly as if it were at its native position, (2) placing a non-native N-glycan on the S3-S4 linker significantly altered function, and (3) placing a non-native N-glycan on the S5-P linker disrupted both trafficking and function. We suggest that Kv1 channels have an N-glycan at a conserved position on only the S1-S2 linker to overcome the constraints for proper folding, trafficking, and function that appear to occur if the N-glycan is moved from this position.
Zhu
Jing
J
Department of Biological Sciences, Fordham University, Bronx, NY 10458, USA.
Recio-Pinto
Esperanza
E
Hartwig
Torsten
T
Sellers
Will
W
Yan
Jingyi
J
Thornhill
William B
WB
D000595:Amino Acid Sequence / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D002462:Cell Membrane / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D003412:Cricetulus; D005110:Extracellular Space / Q000378:metabolism; D006025:Glycosaminoglycans / Q000378:metabolism; D006031:Glycosylation; D051663:Kv1.2 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008564:Membrane Potentials / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D055550:Protein Stability; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D051381:Rats
D006025:Glycosaminoglycans; D051663:Kv1.2 Potassium Channel; D011188:Potassium