Ye Haihong, Kuruvilla Rejji, Zweifel Larry S, Ginty David D
Department of Neuroscience, Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
Neuron. 2003 Jul 3;39(1):57-68. doi: 10.1016/s0896-6273(03)00266-6.
The mechanism by which target-derived Nerve Growth Factor (NGF) signaling is propagated retrogradely, over extremely long distances, to cell bodies to support survival of neurons is unclear. Here we show that survival of sympathetic neurons supported by NGF on distal axons requires the kinase activity of the NGF receptor, TrkA, in both distal axons and cell bodies. In contrast, disruption of TrkA activity exclusively in proximal axonal segments affects neither retrograde NGF-TrkA signaling in cell bodies nor neuronal survival. Ligand-receptor internalization is necessary for survival of neurons supported by NGF on distal axons. Furthermore, antibody neutralization experiments indicate that retrogradely transported NGF, within cell bodies, is critical for neuronal survival but not for growth of distal axons. Taken together, our results indicate that retrogradely transported NGF-TrkA complexes promote sympathetic neuron survival.
由靶源性神经生长因子（NGF）发出的信号是如何在极长的距离上逆行传递至细胞体以维持神经元存活的机制尚不清楚。在此我们表明，由远端轴突上的NGF所支持的交感神经元的存活，在远端轴突和细胞体中都需要NGF受体TrkA的激酶活性。相比之下，仅破坏近端轴突段的TrkA活性，既不影响细胞体中的逆行NGF-TrkA信号传导，也不影响神经元存活。配体-受体内化对于由远端轴突上的NGF所支持的神经元存活是必需的。此外，抗体中和实验表明，在细胞体内逆行运输的NGF对神经元存活至关重要，但对远端轴突的生长则不然。综上所述，我们的结果表明，逆行运输的NGF-TrkA复合物可促进交感神经元存活。
