TY - JOUR
T1 - A novel Kir7.1 splice variant expressed in various mouse tissues shares organisational and functional properties with human Leber amaurosis-causing mutations of this K+ channel
AU - Vera, Erwin
AU - Cornejo, Isabel
AU - Burgos, Johanna
AU - Niemeyer, María Isabel
AU - Sepúlveda, Francisco V.
AU - Cid, L. Pablo
N1 - Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/6/30
Y1 - 2019/6/30
N2 - Kir7.1 is an inwardly rectifying K+ channel present in epithelia where it shares membrane localization with the Na+/K+-pump. In the present communication we report the presence of a novel splice variant of Kir7.1 in mouse tissues including kidney, lung, choroid plexus and retinal pigment epithelium (RPE). The variant named mKir7.1-SV2 lacks most of the C-terminus domain but is predicted to have the two transmembrane domains and permeation pathway unaffected. Similarly truncated predicted proteins, Kir7.1-R166X and Kir7.1-Q219X, would arise from mutations associated with Leber Congenital Amaurosis, a rare recessive hereditary retinal disease that results in vision loss at early age. We found that mKir7.1-SV2 and the pathological variants do not produce any channel activity when expressed alone in HEK-293 cells due to their scarce presence in the plasma membrane. Simultaneous expression with the full length Kir7.1 however leads to a reduction in activity of the wild-type channel that might be due to partial proteasome degradation of WT-mutant channel heteromers.
AB - Kir7.1 is an inwardly rectifying K+ channel present in epithelia where it shares membrane localization with the Na+/K+-pump. In the present communication we report the presence of a novel splice variant of Kir7.1 in mouse tissues including kidney, lung, choroid plexus and retinal pigment epithelium (RPE). The variant named mKir7.1-SV2 lacks most of the C-terminus domain but is predicted to have the two transmembrane domains and permeation pathway unaffected. Similarly truncated predicted proteins, Kir7.1-R166X and Kir7.1-Q219X, would arise from mutations associated with Leber Congenital Amaurosis, a rare recessive hereditary retinal disease that results in vision loss at early age. We found that mKir7.1-SV2 and the pathological variants do not produce any channel activity when expressed alone in HEK-293 cells due to their scarce presence in the plasma membrane. Simultaneous expression with the full length Kir7.1 however leads to a reduction in activity of the wild-type channel that might be due to partial proteasome degradation of WT-mutant channel heteromers.
KW - Kir7.1 channels
KW - Leber congenital amaurosis
KW - Nonsense mutations
KW - Splice variant
UR - http://www.scopus.com/inward/record.url?scp=85065027911&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2019.04.169
DO - 10.1016/j.bbrc.2019.04.169
M3 - Article
C2 - 31056263
AN - SCOPUS:85065027911
SN - 0006-291X
VL - 514
SP - 574
EP - 579
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -