Effects of vanadium(IV) compounds on plasma membrane lipids lead to G protein-coupled receptor signal transduction
Effects of vanadium(IV) compounds on plasma membrane lipids lead to G protein-coupled receptor signal transduction
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DOI：
10.1016/j.jinorgbio.2019.110873
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发表时间：
2020-02-01
影响因子：
3.9
通讯作者：
Crans, Debbie C.
中科院分区：
文献类型：
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作者：
Althumairy, Duaa;Murakami, Heide A.;Crans, Debbie C.
促黄体激素受体（LHR）以生理数量<30，000个受体/细胞表达，在与人绒毛膜促性腺激素（hCG）结合后移位至膜筏并在膜筏内发出信号。类似地，当用双（麦芽酸）氧钒（IV）（BMOV）、双（乙基麦芽酸）氧钒（IV）（BEOV）或VOSO 4处理时，细胞中的LHR信号减少膜脂质堆积。在极化同质转移荧光共振能量转移（homo-FRET）研究中发现过表达的LHR（每个细胞> 85，000个受体）在较大的簇中，不受hCG或钒化合物的影响。细胞内环腺苷酸单磷酸（CAMP）水平表明，只有成簇的LHR是活跃的，并产生细胞内的第二信使，cAMP。当LHR过度表达时，细胞信号传导不受hCG或钒化合物结合的影响。为了确认完整复合物的存在，使用1 mM BMOV、BEOV或VOSO 4获得了细胞培养基中钒化合物的EPR光谱。这些数据被用来确定完整的复杂的10 μ M的解决方案，并通过形态计算验证。BMOV和BEOV样品的影响比钒（IV）水溶液的影响大约两倍，使得完整的钒络合物可能是LHR功能影响的原因。这代表了G蛋白偶联受体激活的新机制;钒化合物在脂质双层中的扰动导致LHR在膜筏结构域中的生理数量的聚集和积累，在膜筏结构域中它们启动信号转导和cAMP（参与信号传导的第二信使）的产生。
Luteinizing hormone receptors (LHR), expressed at physiological numbers < 30,000 receptors per cell, translocate to and signal within membrane rafts following binding of human chorionic gonadotropin (hCG). Similarly LHR signal in cells when treated with bis(maltolato)oxovanadium(IV) (BMOV), bis(ethylmaltolato)oxovanadium (IV) (BEOV) or VOSO4, which decrease membrane lipid packing. Overexpressed LHR (> 85,000 receptors per cell) are found in larger clusters in polarized homo-transfer fluorescence resonance energy transfer (homo-FRET) studies that were not affected by either hCG or vanadium compounds. Intracellular cyclic adenylate mono phosphate (CAMP) levels indicate that only clustered LHR are active and produce the intracellular second messenger, cAMP. When LHR are over-expressed, cell signaling is unaffected by binding of hCG or vanadium compounds. To confirm the existence of intact complex, the EPR spectra of vanadium compounds in cell media were obtained using 1 mM BMOV, BEOV or VOSO4. These data were used to determine intact complex in a 10 mu M solution and verified by speciation calculations. Effects of BMOV and BEOV samples were about two-fold greater than those of aqueous vanadium(IV) making it likely that intact vanadium complex are responsible for effects of LHR function. This represents a new mechanism for activation of a G protein-coupled receptor; perturbations in the lipid bilayer by vanadium compounds lead to aggregation and accumulation of physiological numbers of LHR in membrane raft domains where they initiate signal transduction and production of cAMP, a second messenger involved in signaling.