REEP2 enhances sweet receptor function by recruitment to lipid rafts

Erwin Ilegems, Ken Iwatsuki, Zaza Kokrashvili, Outhiriaradjou Benard, Yuzo Ninomiya, Robert F. Margolskee

Research output: Contribution to journalArticle

31 Scopus citations

Abstract

Heterologously expressed sensory receptors generally do not achieve the ligand sensitivity observed in vivo, and may require specific accessory proteins to ensure optimal function. We searched for taste cell-expressed receptor transporting protein (RTP) and receptor expression enhancing protein (REEP) family members that might serve as accessory molecules to enhance gustatory receptor function. We determined that REEP2 is an integral membrane protein expressed in taste cells, physically associates with both subunits of the type 1 taste receptor 2 and type 1 taste receptor 3 sweet receptor and specifically enhances responses to tastants of heterologously expressed sweet and bitter taste receptors. Downregulation of endogenously expressed REEP2 in the chemosensory enteroendocrine GLUTag cell line dramatically reduced sensitivity of endogenous sweet receptors. In contrast to the observation that RTP1, RTP2, and REEP1 enhance function of olfactory receptors by promoting their transit to the cell surface, we found that REEP2 does not increase cell surface expression of sweet receptors but instead alters their spatial organization. REEP2 recruits sweet receptors into lipid raft microdomains localized near the taste cell's apical region, thereby improving G-protein-coupled receptor signaling and promoting receptor access to tastants arriving through the apical taste pore.

Original languageEnglish (US)
Pages (from-to)13774-13783
Number of pages10
JournalJournal of Neuroscience
Volume30
Issue number41
DOIs
StatePublished - Oct 13 2010
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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    Ilegems, E., Iwatsuki, K., Kokrashvili, Z., Benard, O., Ninomiya, Y., & Margolskee, R. F. (2010). REEP2 enhances sweet receptor function by recruitment to lipid rafts. Journal of Neuroscience, 30(41), 13774-13783. https://doi.org/10.1523/JNEUROSCI.0091-10.2010