Vouyiouklis D A, Brophy P J
Department of Preclinical Veterinary Sciences, University of Edinburgh, Scotland.
J Neurochem. 1997 Sep;69(3):995-1005. doi: 10.1046/j.1471-4159.1997.69030995.x.
Two isoforms of the Ca2+-sensitive, actin-binding protein gelsolin have been identified thus far; one is an intracellular protein, cytoplasmic gelsolin, and the other is a secretory protein called plasma gelsolin. Gelsolin expression in the mammalian CNS appears to be localized mainly to oligodendrocytes where it is presumed that the cytoplasmic isoform predominates. Here, we show that oligodendrocytes not only contain cytoplasmic gelsolin, but they also express a novel gelsolin isoform that we have named gelsolin-3. Cytoplasmic gelsolin, plasma gelsolin, and gelsolin-3 arise by alternative splicing from the same gene. The N-terminal amino acid sequence unique to gelsolin-3 is shown to be encoded by a single exon in a region previously thought to be an intron in the human gelsolin gene. In situ hybridization analysis confirmed that gelsolin-3 mRNA is localized primarily to oligodendrocytes in rat brain. In other tissues, gelsolin-3 shows a more restricted pattern of expression than cytoplasmic gelsolin. These data support the view that the gelsolin isoforms have differential roles in the regulation of the actin cytoskeleton.
到目前为止,已鉴定出两种对钙离子敏感的肌动蛋白结合蛋白凝溶胶蛋白的亚型;一种是细胞内蛋白,即细胞质凝溶胶蛋白,另一种是称为血浆凝溶胶蛋白的分泌蛋白。凝溶胶蛋白在哺乳动物中枢神经系统中的表达似乎主要定位于少突胶质细胞,据推测在这些细胞中细胞质亚型占主导地位。在此,我们表明少突胶质细胞不仅含有细胞质凝溶胶蛋白,而且还表达一种新型的凝溶胶蛋白亚型,我们将其命名为凝溶胶蛋白-3。细胞质凝溶胶蛋白、血浆凝溶胶蛋白和凝溶胶蛋白-3是由同一基因的可变剪接产生的。凝溶胶蛋白-3特有的N端氨基酸序列被证明由人类凝溶胶蛋白基因中一个先前被认为是内含子的区域中的单个外显子编码。原位杂交分析证实凝溶胶蛋白-3 mRNA主要定位于大鼠脑内的少突胶质细胞。在其他组织中,凝溶胶蛋白-3的表达模式比细胞质凝溶胶蛋白更具局限性。这些数据支持这样一种观点,即凝溶胶蛋白亚型在肌动蛋白细胞骨架的调节中具有不同的作用。