Netrins and their receptors
Netrins and their receptors
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DOI：
10.1007/978-0-387-76715-4_2
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发表时间：
2007-01-01
期刊：
影响因子：
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通讯作者：
Kennedy, Timothy E.
中科院分区：
文献类型：
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作者：
Moore, Simon W.;Tessier-Lavigne, Marc;Kennedy, Timothy E.
Netrins 是在发育过程中指导细胞和轴突迁移的蛋白质家族。除了两种 GPI 锚定膜蛋白 netrin-G1 和 G2 之外，在哺乳动物中还发现了三种分泌性 netrin（netrin-1、-3 和 -4）。 netrin-1 的直系同源物在脊椎动物和一些双侧对称无脊椎动物发育中的中枢神经系统中线发挥着高度保守的指导作用。在脊椎动物中，胚胎神经管腹侧中线的底板细胞分泌 netrin-1，在神经上皮中产生 netrin 蛋白的圆周梯度。这种蛋白质梯度具有双功能，将一些轴突吸引到中线并排斥其他轴突。分泌性 netrin 的受体包括 DCC（在结直肠癌中缺失）和 UNC5 同源物：哺乳动物中的 UNC5A、B、C 和 D。 DCC 介导化学吸引，而排斥则需要 UNC5 同源物，在某些情况下还需要 DCC。 netrin-G 蛋白结合 NGL（netrin G 配体），这是与 DCC 或 UNC5 同源物无关的单次跨膜蛋白。 Netrin 的功能不仅限于发育中的中枢神经系统中线。各种网络蛋白引导细胞和轴突在整个胚胎中枢神经系统中迁移，并且在某些情况下继续在成熟神经系统中表达。此外，虽然最初确定其具有引导轴突的能力，但现在已在神经系统之外确定了 netrin 的功能作用，它们通过指导细胞迁移和调节细胞与细胞以及细胞与基质的粘附来影响组织形态发生。
Netrins are a family of proteins that direct cell and axon migration during development. Three secreted netrins (netrin-1, -3 and -4) have been identified in mammals, in addition to two GPI-anchored membrane proteins, netrin-G1 and G2. Orthologues of netrin-1 play a highly conserved role as guidance cues at the midline of the developing CNS of vertebrates and some bilaterally symmetric invertebrates. In vertebrates, floor plate cells at the ventral midline of the embryonic neural tube secrete netrin-1, generating a circumferential gradient of netrin protein in the neuroepithelium. This protein gradient is bifunctional, attracting some axons to the midline and repelling others. Receptors for the secreted netrins include DCC (deleted in colorectal cancer) and the UNC5 homologues: UNC5A, B, C and D in mammals. DCC mediates chemoattraction, while repulsion requires an UNC5 homologue and, in some cases, DCC. The netrin-G proteins bind NGLs (netrin G ligands), single pass transmembrane proteins unrelated to either DCC or the UNC5 homologues. Netrin function is not limited to the developing CNS midline. Various netrins direct cell and axon migration throughout the embryonic CNS, and in some cases continue to be expressed in the mature nervous system. Furthermore, although initially identified for their ability to guide axons, functional roles for netrins have now been identified outside the nervous system where they influence tissue morphogenesis by directing cell migration and regulating cell-cell and cell-matrix adhesion.