TY - JOUR
T1 - The Kv1.2 potassium channel
T2 - The position of an N-glycan on the extracellular linkers affects its protein expression and function
AU - Zhu, Jing
AU - Recio-Pinto, Esperanza
AU - Hartwig, Torsten
AU - Sellers, Will
AU - Yan, Jingyi
AU - Thornhill, William B.
N1 - Funding Information:
This research was supported by National Institutes of Health Grant USA NS048906 (W.B.T.) and the American Heart Association with a Grant-in-Aid. (W.B.T).
PY - 2009/1/28
Y1 - 2009/1/28
N2 - 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.
AB - 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.
KW - Activation
KW - N-glycans
KW - Potassium channel
KW - Protein stability
KW - Trafficking
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U2 - 10.1016/j.brainres.2008.11.033
DO - 10.1016/j.brainres.2008.11.033
M3 - Article
C2 - 19056359
AN - SCOPUS:58149382415
SN - 0006-8993
VL - 1251
SP - 16
EP - 29
JO - Brain research
JF - Brain research
ER -