Ichinose T, Snider W D
CSNSI, Department of Neurology, Washington University School of Medicine, St. Louis, Missouri, USA.
J Neurosci Res. 2000 Feb 1;59(3):365-71. doi: 10.1002/(sici)1097-4547(20000201)59:3<365::aid-jnr10>3.0.co;2-i.
Neurotrophins are powerful regulators of neuronal morphology. Several lines of evidence are consistent with the idea that characteristic axonal and dendritic morphologies throughout the nervous system may be determined by local patterns of neurotrophin and neurotrophin receptor expression. Neurotrophin receptor tryosine kinases (Trks) exist in both tyrosine-containing (TK+) and tyrosine-lacking (TK-) isoforms, both of which are expressed in many neuronal populations. However, ratios of TK+ to TK- isoforms may vary at different stages of development and may be differentially distributed to cellular compartments. To test whether these isoforms have different functions related to axon outgrowth, full-length or tyrosine kinase-lacking TrkC receptors were overexpressed in embryonic dorsal root ganglion neurons maintained in explant cultures in neurotrophin-3 (NT-3)-containing media. Neurons were transfected with plasmid DNA encoding enhanced yellow fluorescent protein (EYFP) and TrkC receptor isoforms by particle-mediated gene transfer. Control neurons possessed 3.7 +/- 1.3 primary processes and 113.8 +/- 46 branch points. About 80% of the branches were located along the distal part of the axon. Transfection with the trkC TK+ increased the number of primary processes (6.5 +/- 2.8), whereas transfection with trkC TK- reduced the formation of primary processes (3.0 +/- 1.3). Surprisingly, the distribution of branch points was shifted to the proximal region of axons in neurons transfected with trkC TK-. These observations are consistent with the idea that differential expression of Trk isoforms during development may sculpt axonal morphology.
神经营养因子是神经元形态的强大调节因子。多项证据支持这样一种观点，即整个神经系统中特征性的轴突和树突形态可能由神经营养因子和神经营养因子受体表达的局部模式所决定。神经营养因子受体酪氨酸激酶（Trks）以含酪氨酸（TK+）和不含酪氨酸（TK-）的异构体形式存在，二者均在许多神经元群体中表达。然而，TK+与TK-异构体的比例在发育的不同阶段可能会有所不同，并且可能在细胞区室中呈差异分布。为了测试这些异构体是否具有与轴突生长相关的不同功能，将全长或缺乏酪氨酸激酶的TrkC受体在含有神经营养因子-3（NT-3）的培养基中维持的外植体培养的胚胎背根神经节神经元中过表达。通过粒子介导的基因转移，用编码增强型黄色荧光蛋白（EYFP）和TrkC受体异构体的质粒DNA转染神经元。对照神经元有3.7±1.3个初级突起和113.8±46个分支点。约80%的分支位于轴突的远端部分。用trkC TK+转染增加了初级突起的数量（6.5±2.8），而用trkC TK-转染则减少了初级突起的形成（3.0±1.3）。令人惊讶的是，在用trkC TK-转染的神经元中，分支点的分布转移到了轴突的近端区域。这些观察结果与发育过程中Trk异构体的差异表达可能塑造轴突形态的观点一致。
