Tsui-Pierchala Brian A, Milbrandt Jeffrey, Johnson Eugene M
Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Neuron. 2002 Jan 17;33(2):261-73. doi: 10.1016/s0896-6273(01)00585-2.
During postnatal development, sympathetic neurons lose their dependence upon NGF for survival but continue to require NGF for soma and process growth and for development of a mature neurotransmitter phenotype. Although c-Ret is expressed in sympathetic neurons during this period, its function in these transitional processes is unclear. The level of Ret phosphorylation markedly increased with postnatal age in SCG neurons in vitro and in vivo. Postnatal Ret phosphorylation did not require either GFLs or GFR(alpha) coreceptors. Instead, NGF promoted age-dependent Ret phosphorylation with delayed kinetics both in vitro and in vivo. Functionally, maximal NGF-dependent trophism of mature sympathetic neurons required Ret, but not GFR(alpha) coreceptors. Therefore, NGF promotes phosphorylation of the heterologous RTK Ret resulting in augmented growth, metabolism, and gene expression.
在出生后的发育过程中，交感神经元失去了对神经生长因子（NGF）的生存依赖，但仍需要NGF来支持胞体和突起的生长以及成熟神经递质表型的发育。尽管在此期间c-Ret在交感神经元中表达，但其在这些过渡过程中的功能尚不清楚。在体外和体内，颈上神经节（SCG）神经元中Ret磷酸化水平随出生后年龄显著增加。出生后的Ret磷酸化既不需要胶质细胞源性神经营养因子（GFLs）也不需要GFR(α)共受体。相反，NGF在体外和体内均以延迟动力学促进年龄依赖性的Ret磷酸化。在功能上，成熟交感神经元的最大NGF依赖性营养作用需要Ret，但不需要GFR(α)共受体。因此，NGF促进异源受体酪氨酸激酶Ret的磷酸化，从而增强生长、代谢和基因表达。
