Stamm S, Casper D, Hanson V, Helfman D M
Max-Planck-Institute of Neurobiology, Am Klopferspitz 18a, D-82152 Martinsried, Germany.
Brain Res Mol Brain Res. 1999 Jan 22;64(1):108-18. doi: 10.1016/s0169-328x(98)00313-1.
Clathrin light chain B (LCB) is a major component of clathrin coated vesicles, which are structures involved in intracellular transport. A neuron-specific isoform of LCB is generated by incorporation of a single exon (EN) using an alternative splicing mechanism that reflects the special demands of neurons, such as axonal transport and synaptic neurotransmission. Here, we demonstrate that this neuron-specific exon is developmentally regulated and is excluded in non-neuronal cells because its 5' and 3' splice sites deviate from the mammalian consensus sequences. A gel retardation assay indicated the presence of a developmentally regulated factor in brain that binds to the neuronal exon. In addition, EN usage is repressed by increasing the concentration of htra2-beta1, a splice factor whose isoform expression is influenced by neuronal activity. We propose that a brain-specific factor is involved in EN recognition during development and adulthood. In addition, ubiquitously expressed splicing factors such as htra2-beta1 are involved in regulating EN expression in the adult brain.
网格蛋白轻链B（LCB）是网格蛋白包被小泡的主要成分，这些小泡是参与细胞内运输的结构。通过使用反映神经元特殊需求（如轴突运输和突触神经传递）的可变剪接机制并入单个外显子（EN），产生了一种神经元特异性的LCB异构体。在这里，我们证明这种神经元特异性外显子在发育过程中受到调控，并且在非神经元细胞中被排除，因为其5'和3'剪接位点偏离了哺乳动物的共有序列。凝胶阻滞试验表明，大脑中存在一种与神经元外显子结合的发育调控因子。此外，通过增加htra2-beta1（一种剪接因子，其异构体表达受神经元活动影响）的浓度，EN的使用受到抑制。我们提出，一种大脑特异性因子在发育和成年期参与EN识别。此外，诸如htra2-beta1等普遍表达的剪接因子参与调节成人大脑中的EN表达。
