Fruttiger M, Calver A R, Richardson W D
Wolfson Institute for Biomedical Research and Department of Biology, University College London, UK.
Curr Biol. 2000 Oct 19;10(20):1283-6. doi: 10.1016/s0960-9822(00)00757-0.
Neurons synthesise and secrete many growth and survival factors but it is not usually clear whether they are released locally at the cell body or further afield from axons or axon terminals. Without this information, we cannot predict the site(s) of action or the biological functions of many neuron-derived factors. For example, can neuronal platelet-derived growth factor (PDGF) be secreted from axons and reach glial cells in nerve-fibre (white-matter) tracts? To address this question, we expressed PDGF-A in retinal ganglion neurons in transgenic mice and tested for release of PDGF from cell bodies in the retina and from axons in the optic nerve. In both the retina and optic nerve, there are glial cells that express PDGF receptor alpha (PDGFR alpha) [1] and divide in response to PDGF [2-5], so we could detect functional PDGF indirectly through the mitogenic response of glia at both locations. Expressing PDGF-A in neurons under the control of the neuron-specific enolase promoter (NSE-PDGF-A) resulted in a striking hyperplasia of retinal astrocytes, demonstrating that PDGF is secreted from the cell bodies of neurons in the retina [4]. In contrast, glial proliferation in the optic nerve was unaffected, indicating that PDGF is not released from axons. When PDGF was expressed directly in the optic nerve under the control of an astrocyte-specific promoter (GFAP-PDGF-A), oligodendrocyte progenitors hyperproliferated, resulting in a hypertrophic optic nerve. We conclude that PDGF is constitutively secreted from neuronal cell bodies in vivo, but not from axons in white-matter tracts.
神经元合成并分泌多种生长和存活因子，但通常并不清楚它们是在细胞体局部释放，还是从轴突或轴突终末释放到更远的地方。没有这些信息，我们就无法预测许多神经元衍生因子的作用位点或生物学功能。例如，神经元源性血小板衍生生长因子（PDGF）能否从轴突分泌并到达神经纤维（白质）束中的胶质细胞？为了解决这个问题，我们在转基因小鼠的视网膜神经节神经元中表达了PDGF-A，并检测了视网膜中细胞体和视神经轴突释放的PDGF。在视网膜和视神经中，都有表达PDGF受体α（PDGFRα）的胶质细胞[1]，并且会对PDGF产生反应而增殖[2-5]，所以我们可以通过这两个部位胶质细胞的促有丝分裂反应间接检测功能性PDGF。在神经元特异性烯醇化酶启动子（NSE-PDGF-A）的控制下，在神经元中表达PDGF-A导致视网膜星形胶质细胞显著增生，这表明PDGF是从视网膜中神经元的细胞体分泌的[4]。相比之下，视神经中的胶质细胞增殖未受影响，这表明PDGF不是从轴突释放的。当在星形胶质细胞特异性启动子（GFAP-PDGF-A）的控制下直接在视神经中表达PDGF时，少突胶质前体细胞过度增殖，导致视神经肥大。我们得出结论，在体内，PDGF是由神经元细胞体组成性分泌的，而不是由白质束中的轴突分泌。
