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.

Autor: Vera E; Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile., Cornejo I; Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile., Burgos J; Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile., Niemeyer MI; Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile., Sepúlveda FV; Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile., Cid LP; Centro de Estudios Científicos (CECs), Avenida Arturo Prat 514, Valdivia, Chile. Electronic address: pcid@cecs.cl.
Jazyk: angličtina
Zdroj: Biochemical and biophysical research communications [Biochem Biophys Res Commun] 2019 Jun 30; Vol. 514 (3), pp. 574-579. Date of Electronic Publication: 2019 May 03.
DOI: 10.1016/j.bbrc.2019.04.169
Abstrakt: 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.
(Copyright © 2019 Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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