Kumanogoh Haruko, Asami Junko, Nakamura Shun, Inoue Takayoshi
Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan.
Mol Cell Neurosci. 2008 Nov;39(3):465-77. doi: 10.1016/j.mcn.2008.07.024. Epub 2008 Aug 9.
A brain-derived neurotrophic factor (BDNF) receptor TrkB involves three spliced variants, namely the tyrosine kinase domain (TK) intact (+) and two TK(-) isoforms T1 and T2, yet their precise roles are largely unknown. Here we extensively map the mRNA expression patterns of BDNF and TrkB variants, further to gain insights in TK(-) specific functions during mouse development. Consequently, we found that TK(+), T1 and T2 were expressed in distinct regions of the mouse nervous system at the embryonic and postnatal stages, implicating separable functions of TK(-) forms. Additionally we uncovered five expressed segments in the intron between T2 and T1 specific exons, and one of these segments was revealed to code novel TK(-) receptors with unique responsiveness in vitro. These results suggest dynamic modes of expression from the Ntrk2 gene locus and multiple roles of TK(-) forms in the developing mouse nervous system.
脑源性神经营养因子（BDNF）受体TrkB有三种剪接变体，即酪氨酸激酶结构域（TK）完整的（+）型以及两种TK（-）亚型T1和T2，但其确切作用很大程度上尚不清楚。在此，我们广泛绘制了BDNF和TrkB变体的mRNA表达模式，以进一步深入了解小鼠发育过程中TK（-）的特定功能。结果，我们发现TK（+）、T1和T2在胚胎期和出生后小鼠神经系统的不同区域表达，这暗示了TK（-）形式具有可分离的功能。此外，我们在T2和T1特异性外显子之间的内含子中发现了五个表达片段，其中一个片段被揭示可编码在体外具有独特反应性的新型TK（-）受体。这些结果表明Ntrk2基因座的动态表达模式以及TK（-）形式在发育中的小鼠神经系统中的多种作用。
