Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different consequences in potassium channel function.

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Citation

Pabon A, Chan KW, Sui JL, Wu X, Logothetis DE, Thornhill WB

Glycosylation of GIRK1 at Asn119 and ROMK1 at Asn117 has different consequences in potassium channel function.

J Biol Chem. 2000 Sep 29;275(39):30677-82.

PubMed ID
10889209 [ View in PubMed
]
Abstract

GIRK (G protein-gated inward rectifier K(+) channel) proteins play critical functional roles in heart and brain physiology. Using antibodies directed to either GIRK1 or GIRK4, site-directed mutagenesis, and specific glycosidases, we have investigated the effects of glycosylation in the biosynthesis and heteromerization of these proteins expressed in oocytes. Both GIRK1 and GIRK4 have one extracellular consensus N-glycosylation site. Using chimeras between GIRK1 and GIRK4 as well as a GIRK1 N-glycosylation mutant, we report that GIRK1 was glycosylated at Asn(119), whereas GIRK4 was not glycosylated at Asn(132). GIRK1 membrane-spanning domain 1 was required for optimal glycosylation at Asn(119) because a chimera that contained GIRK4 membrane-spanning domain 1 significantly reduced the addition of a carbohydrate structure at this site. This finding may partly account for the reason that GIRK4 is not glycosylated at Asn(132), either as a homomer or when coexpressed with GIRK1. When the GIRK1(N119Q) mutant was coexpressed with GIRK4, the biophysical properties of the heteromeric channel and the magnitude of the agonist-induced currents were similar to those of controls. Thus, N-glycosylation of GIRK1 at Asn(119) does not appear to affect its physical association with GIRK4, the routing of the heteromer to the cell surface, or heteromeric channel function, unlike the dramatic functional effects of N-glycosylation of ROMK1 at Asn(117) (Schwalbe, R. A., Wang, Z., Wible, B. A., and Brown, A. M. (1995) J. Biol. Chem. 270, 15336-15340).

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
ATP-sensitive inward rectifier potassium channel 1P48048Details
G protein-activated inward rectifier potassium channel 1P48549Details