Lysophospholipid receptors: Implications for neural signaling
Lysophospholipid receptors: Implications for neural signaling
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DOI：
10.1615/critrevneurobiol.v13.i2.20
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Chun, J
中科院分区：
文献类型：
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作者：
Chun, J
溶血磷脂（LP），如溶血磷脂酸（LPA）和鞘氨醇-1-磷酸（S1 P）代表数量较少的磷脂物质，但能够作为细胞外信号。作为一个由脂质主导的器官系统，神经系统似乎是这种形式的细胞间信号传导的受益者。然而，确定这些脂质的神经生物学重要性的主要困难是缺乏克隆受体。这些受体的不可用性，实际上，不确定的存在，已经特别成问题，因为缺乏特异性的，竞争性拮抗剂来阻断功能。此外，这些脂质具有洗涤剂样的化学结构，提出了解释，即任何观察到的外源性应用溶血磷脂的影响可能是由于非特异性膜扰动。在涉及大脑皮层神经发生的G蛋白偶联受体（GPCR）基因的研究中，分离出第一个溶血磷脂受体基因（lp（A1）/vzg-1）（Hecht et al.，细胞生物学杂志，135，1071，1996），暗示受体介导的溶血磷脂信号传导是神经系统发育和功能的潜在重要组分。表达研究表明在神经发生、皮质发育中的作用，以及对神经胶质细胞，特别是少突胶质细胞和雪旺细胞发育的影响。本文综述了LP受体的分子生物学、细胞内信号传导的相关方面及其在神经系统中的可能作用。
Lysophospholipids (LPs) such as lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) represent quantitatively minor phospholipid species that nonetheless are capable of acting as extracellular signals. As an organ system dominated by lipids, the nervous system would seem a likely benefactor of this form of intercellular signaling. A major difficulty in determining the neurobiological importance of these lipids, however, has been a lack of cloned receptors. The unavailability, indeed, uncertain existence, of these receptors has been particularly problematic because of the absence of specific, competitive antagonists to block function. Further, these lipids have detergent-like chemical structures, raising the explanation that any observed effects of exogenously applied lysophospholipids could be due to nonspecific membrane perturbations. During studies of G-protein coupled receptor (GPCR) genes involved with cerebral cortical neurogenesis, the first lysophospholipid receptor gene (lp(A1)/vzg-1) was isolated (Hecht et al., J. Cell Biol., 135, 1071, 1996), implicating receptor-mediated lysophospholipid signaling as potentially important components of nervous system development and function. Expression studies indicated roles in neurogenesis, cortical development, and effects on glia, particularly oligodendrocyte and Schwann cell development. Reviewed here are the molecular biology of LP receptors, relevant aspects of intracellular signaling, and their possible roles in the nervous system.