Structural determinants for membrane trafficking and G protein selectivity of a mouse olfactory receptor

Sayako Katada, Motonari Tanaka, Kazushige Touhara

研究成果: Contribution to journalArticle査読

62 被引用数 (Scopus)

抄録

The G protein-coupled olfactory receptor (OR) superfamily plays a critical role in recognizing a broad range of odorants. Each OR appears to recognize odorants based on similarities in molecular structures such that mOR-EG, a mouse OR, binds eugenol, vanillin, and some other structurally related odorants. Only a few ORs, however, have been characterized functionally due to the difficulties in expressing ORs in heterologous cells. In this report, we demonstrate roles of the N- and C-terminal domains as key elements in the functional expression and signal transducing activity of an OR. Disruption of the N-terminal glycosylation site of the mOR-EG completely impaired its membrane trafficking to the cell surface. Functional expression of the mOR-EG was greatly enhanced by addition of extra N-terminal glycosylation sequences. Addition of a C-terminal epitope-tag or C-terminal truncation significantly reduced the odorant-response activity, although the receptors were properly targeted to the plasma membrane. Analysis of a series of truncated ORs revealed a region in the C-terminus that was crucial for the receptor activity. Replacement of the C-terminal portion of the mOR-EG with that of rhodopsin disrupted the coupling to Gαs but not to Gα15, demonstrating that the C-terminus is involved in regulating G protein specificity. These results suggest that glycosylation of the N-terminal portion is critical for OR expression and membrane trafficking, while the C-terminal portion plays a role in defining proper conformation, which, in turn, specifies the G protein selectivity of the OR. This information helps clarify the mechanisms that regulate membrane trafficking and G protein interaction of the OR superfamily.

本文言語英語
ページ(範囲)1453-1463
ページ数11
ジャーナルJournal of Neurochemistry
90
6
DOI
出版ステータス出版済み - 9 2004
外部発表はい

All Science Journal Classification (ASJC) codes

  • 生化学
  • 細胞および分子神経科学

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