betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system.
betaIV spectrin, a new spectrin localized at axon initial segments and nodes of ranvier in the central and peripheral nervous system.
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DOI：
10.1083/jcb.151.5.985
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发表时间：
2000-11-27
影响因子：
7.8
通讯作者：
Solimena, M
中科院分区：
文献类型：
--
作者：
Berghs, S;Aggujaro, D;Dirkx, R Jr;Maksimova, E;Stabach, P;Hermel, J M;Zhang, J P;Philbrick, W;Slepnev, V;Ort, T;Solimena, M
我们报道了βIV血影蛋白的鉴定，它是一种新的血影蛋白，是作为受体酪氨酸磷酸酶样蛋白ICA512的相互作用而分离出来的。βIV血影蛋白基因分别位于人和小鼠染色体19q13.13和7B2上。βIV血影蛋白的选择性剪接至少产生四种不同的亚型，编号为βIVΣ1-βIVΣ4血影蛋白。最长的异构体(βIVΣ1 SPECTIN)包括一个肌动蛋白结合域，接着是17个SPECTIN重复序列，一个氨基酸序列重复4次的特定结构域，几个可能的SH3结合位点和一个Pleckstrin同源结构域。βIVΣ2和βIVΣ3光谱蛋白分别包含βIVΣ1光谱蛋白的氨基末端和羧基末端，而βIVΣ4光谱蛋白缺乏ERQES和Pleckstrin同源结构域。Northern杂交结果显示，βIV血影蛋白转录本在脑和胰岛中大量表达。免疫印迹分析表明，βIVΣ1是一种分子量为250kD的蛋白。抗βIV血影蛋白抗体还与另外两个160kD和140kD的异构体发生反应。这些异构体在亚细胞分级、洗涤剂可萃取性和磷酸化方面与βIVΣ1血影蛋白的分布不同。在胰岛中，βIV血影蛋白在α中的免疫反应比在β细胞中更明显。在脑内，βIV血影蛋白主要分布在有髓神经元中，与骨架蛋白G480/2 70-KD共定位于轴突起始段和神经节。同样，在大鼠坐骨神经中，βIV血影蛋白主要集中在兰维尔结节。在大鼠的海马体中，从胚胎第19天起就可以检测到βIVΣ1的血影蛋白，并伴随着起始节段的免疫反应的出现。因此，我们认为βIVΣ1与骨架G480/270-KD相互作用，参与电压门控Na+通道和细胞黏附分子在兰维尔起始节段和结节的聚集。
We report the identification of βIV spectrin, a novel spectrin isolated as an interactor of the receptor tyrosine phosphatase-like protein ICA512. The βIV spectrin gene is located on human and mouse chromosomes 19q13.13 and 7b2, respectively. Alternative splicing of βIV spectrin generates at least four distinct isoforms, numbered βIVΣ1–βIVΣ4 spectrin. The longest isoform (βIVΣ1 spectrin) includes an actin-binding domain, followed by 17 spectrin repeats, a specific domain in which the amino acid sequence ERQES is repeated four times, several putative SH3-binding sites and a pleckstrin homology domain. βIVΣ2 and βIVΣ3 spectrin encompass the NH2- and COOH-terminal halves of βIVΣ1 spectrin, respectively, while βIVΣ4 spectrin lacks the ERQES and the pleckstrin homology domain. Northern blots revealed an abundant expression of βIV spectrin transcripts in brain and pancreatic islets. By immunoblotting, βIVΣ1 spectrin is recognized as a protein of 250 kD. Anti–βIV spectrin antibodies also react with two additional isoforms of 160 and 140 kD. These isoforms differ from βIVΣ1 spectrin in terms of their distribution on subcellular fractionation, detergent extractability, and phosphorylation. In islets, the immunoreactivity for βIV spectrin is more prominent in α than in β cells. In brain, βIV spectrin is enriched in myelinated neurons, where it colocalizes with ankyrinG 480/270-kD at axon initial segments and nodes of Ranvier. Likewise, βIV spectrin is concentrated at the nodes of Ranvier in the rat sciatic nerve. In the rat hippocampus, βIVΣ1 spectrin is detectable from embryonic day 19, concomitantly with the appearance of immunoreactivity at the initial segments. Thus, we suggest that βIVΣ1 spectrin interacts with ankyrinG 480/270-kD and participates in the clustering of voltage-gated Na+ channels and cell-adhesion molecules at initial segments and nodes of Ranvier.