Sensing of lysophospholipids by TRPC5 calcium channel
Sensing of lysophospholipids by TRPC5 calcium channel
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DOI：
10.1074/jbc.m510301200
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发表时间：
2006-02-24
影响因子：
4.8
通讯作者：
Beech, DJ
中科院分区：
文献类型：
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作者：
Flemming, PK;Dedman, AM;Beech, DJ
TRPC钙通道是脊椎动物细胞中普遍存在的一个特征，但由于对内源性调节剂的激活机制和身份的了解有限，对它们的理解受到阻碍。我们已经发现，TRPC通道之一，TRPC5，强烈激活常见的内源性溶血磷脂，包括溶血磷脂酰胆碱（LPC），但相比之下，不花生四烯酸。虽然TRPC5被G蛋白偶联受体激动剂刺激，但LPC对TRPC5的激活发生在下游，且独立于G蛋白信号传导。这种效果不是由于活性氧的产生，也不是由于LPC的去污效果。LPC激活TRPC5时，适用于切除的膜补丁，因此有一个相对直接的行动上的通道结构，无论是因为通道上的磷脂结合位点，或因为敏感性的通道扰动的双层某些脂质。活化显示依赖于侧链长度和化学头基。这些数据揭示了TRPC 5先前未被认识到的溶血磷脂敏感能力，该能力赋予了脂质离子型受体的性质。
TRPC calcium channels are emerging as a ubiquitous feature of vertebrate cells, but understanding of them is hampered by limited knowledge of the mechanisms of activation and identity of endogenous regulators. We have revealed that one of the TRPC channels, TRPC5, is strongly activated by common endogenous lysophospholipids including lysophosphatidylcholine ( LPC) but, by contrast, not arachidonic acid. Although TRPC5 was stimulated by agonists at G-protein-coupled receptors, TRPC5 activation by LPC occurred downstream and independently of G-protein signaling. The effect was not due to the generation of reactive oxygen species or because of a detergent effect of LPC. LPC activated TRPC5 when applied to excised membrane patches and thus has a relatively direct action on the channel structure, either because of a phospholipid binding site on the channel or because of sensitivity of the channel to perturbation of the bilayer by certain lipids. Activation showed dependence on side-chain length and the chemical head-group. The data revealed a previously unrecognized lysophospholipid-sensing capability of TRPC5 that confers the property of a lipid ionotropic receptor.