Garner A S, Menegay H J, Boeshore K L, Xie X Y, Voci J M, Johnson J E, Large T H
Department of Neurosciences, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106-4975, USA.
J Neurosci. 1996 Mar 1;16(5):1740-52. doi: 10.1523/JNEUROSCI.16-05-01740.1996.
The expression of novel TrkB receptor transcripts has been characterized to understand the potentially diverse roles of brain-derived neurotrophic factor (BDNF) in the developing avian visual system. In situ localization with an extracellular domain probe common to all TrkB transcripts labeled a sub-population of large retinal ganglion cells as well as many associated visual nuclei, including the neuronal layers within the tectum that receive retinal innervation. Because of the potential for structurally and functionally distinct receptors derived from the TrkB gene locus, cDNA cloning and reverse transcription-PCR analysis were used to further analyze receptor isoform expression in the retina and tectum. Receptor isoforms were sequenced that contained a deletion of the N terminus, a deletion in the putative ligand-binding domain, or a deletion in the cytoplasmic juxtamembrane (JM) domain. Two novel JM insertion sequences also were identified, one of which exhibits weak homology to beta-actin and was found in both kinase-containing (TK+) and kinase deletion (KD) receptor isoforms. In the developing retina, TK+ receptor mRNA is upregulated during the period of retinal ganglion cell (RGC) death, consistent with the proposed role of BDNF as a tectal-derived survival factor for RGCs. However, the expression of TK+ transcripts in the tectum indicates that this structure also contains cells responsive to BDNF throughout development. Because BDNF is expressed in both the retina and tectum, it is conceivable that TrkB also mediates autocrine/paracrine signaling within these structures or anterograde retinotectal trophic support.
为了解脑源性神经营养因子（BDNF）在发育中的鸟类视觉系统中可能具有的多种作用，研究人员对新型TrkB受体转录本的表达进行了表征。使用针对所有TrkB转录本共有的细胞外结构域探针进行原位定位，标记出了一部分大型视网膜神经节细胞以及许多相关的视觉核团，包括接受视网膜神经支配的顶盖内的神经元层。由于TrkB基因座可能产生结构和功能不同的受体，因此利用cDNA克隆和逆转录PCR分析进一步研究视网膜和顶盖中受体亚型的表达。对含有N端缺失、假定配体结合结构域缺失或细胞质近膜（JM）结构域缺失的受体亚型进行了测序。还鉴定出了两个新的JM插入序列，其中一个与β-肌动蛋白具有弱同源性，并且在含激酶（TK+）和激酶缺失（KD）受体亚型中均有发现。在发育中的视网膜中，TK+受体mRNA在视网膜神经节细胞（RGC）死亡期间上调，这与BDNF作为源自顶盖的RGC存活因子的作用一致。然而，TK+转录本在顶盖中的表达表明，在整个发育过程中，该结构也包含对BDNF有反应的细胞。由于BDNF在视网膜和顶盖中均有表达，可以推测TrkB也介导这些结构内的自分泌/旁分泌信号传导或顺行性视网膜顶盖营养支持。
