REEP2 enhances sweet receptor function by recruitment to lipid rafts.
REEP2 enhances sweet receptor function by recruitment to lipid rafts.
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DOI：
10.1523/jneurosci.0091-10.2010
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发表时间：
2010-10-13
期刊：
影响因子：
--
通讯作者：
Margolskee RF
中科院分区：
文献类型：
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作者：
Ilegems E;Iwatsuki K;Kokrashvili Z;Benard O;Ninomiya Y;Margolskee RF
异源表达的感觉受体通常不能达到体内观察到的配体敏感性，并且可能需要特定的辅助蛋白来确保最佳功能。我们寻找味觉细胞表达的受体转运蛋白（RTP）和受体表达增强蛋白（REEP）家族成员，可能作为辅助分子，以加强味觉受体功能。我们确定REEP 2是在味觉细胞中表达的一种完整的膜蛋白，与1型味觉受体2和1型味觉受体3甜味受体的两个亚基物理相关，并且特异性地增强对异源表达的甜味和苦味受体的促味剂的反应。在化学感受性肠内分泌GLUTag细胞系中内源性表达的REEP 2的下调显著降低了内源性甜味受体的敏感性。与RTP1、RTP2和REEP 1通过促进嗅觉受体转运到细胞表面来增强嗅觉受体功能的观察相反，我们发现REEP 2并不增加甜味受体的细胞表面表达，而是改变了它们的空间组织。REEP 2将甜味受体募集到位于味觉细胞顶端区域附近的脂筏微结构域中，从而改善G蛋白偶联受体信号传导并促进受体接近通过顶端味觉孔到达的促味剂。
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.