NDLI: G protein–coupled receptors differentially regulate glycosylation and activity of the inwardly rectifying potassium channel Kir7.1

Content Provider	Journal of Biological Chemistry (JBC)
Author	Carrington, Sheridan J. Hernandez, Ciria C. Swale, Daniel R. Aluko, Oluwatosin A. Denton, Jerod S. Cone, Roger D.
Abstract	Kir7.1 is an inwardly rectifying potassium channel with important roles in the regulation of the membrane potential in retinal pigment epithelium, uterine smooth muscle, and hypothalamic neurons. Regulation of G protein–coupled inwardly rectifying potassium (GIRK) channels by G protein–coupled receptors (GPCRs) via the G protein βγ subunits has been well characterized. However, how Kir channels are regulated is incompletely understood. We report here that Kir7.1 is also regulated by GPCRs, but through a different mechanism. Using Western blotting analysis, we observed that multiple GPCRs tested caused a striking reduction in the complex glycosylation of Kir7.1. Further, GPCR-mediated reduction of Kir7.1 glycosylation in HEK293T cells did not alter its expression at the cell surface but decreased channel activity. Of note, mutagenesis of the sole Kir7.1 glycosylation site reduced conductance and open probability, as indicated by single-channel recording. Additionally, we report that the L241P mutation of Kir7.1 associated with Lebers congenital amaurosis (LCA), an inherited retinal degenerative disease, has significantly reduced complex glycosylation. Collectively, these results suggest that Kir7.1 channel glycosylation is essential for function, and this activity within cells is suppressed by most GPCRs. The melanocortin-4 receptor (MC4R), a GPCR previously reported to induce ligand-regulated activity of this channel, is the only GPCR tested that does not have this effect on Kir7.1.
Related Links	http://www.jbc.org/content/293/46/17739.abstract
Ending Page	17753
Starting Page	17739
Page Count	15
File Format	HTM / HTML PDF
ISSN	00219258
Journal	Journal of Biological Chemistry (JBC)
Issue Number	46
Volume Number	293
DOI	10.1074/jbc.RA118.003238
e-ISSN	1083351X
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2018-11-16
Access Restriction	Open
Subject Keyword	Ion channel G protein–coupled receptor (GPCR) Potassium channel Glycosylation Signal transduction Signal Transduction
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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