Sontag J M, Fykse E M, Ushkaryov Y, Liu J P, Robinson P J, Südhof T C
Department of Molecular Genetics, University of Texas Southwestern Medical Center, Dallas 75235.
J Biol Chem. 1994 Feb 11;269(6):4547-54.
Dynamin is a GTP-, microtubule-, and phospholipid-binding protein that is expressed primarily in brain. In Drosophila, the shibire gene encodes a homologue of dynamin; mutations in this gene result in a defect in endocytosis, suggesting a function for dynamin in endocytic membrane traffic. In the present study we show that there are at least two distinct dynamin genes in mammals whose products are referred to as dynamins I and II. The two dynamins are similar to each other (79% identity) and are both equally homologous to the Drosophila shibire gene product (66% identity). The highest degree of identity between dynamins is observed in their N-terminal halves, whereas their C termini exhibit little homology. Transcripts of both dynamin genes are subject to at least two alternative splicing events, the first of which is identically found in both dynamins, whereas the second site of alternative splicing is different between the two types of dynamins. The first alternatively spliced sequence of the dynamins consists of an interior region that is present in two distinct but homologous forms in both dynamins, suggesting alternative use of exons in both genes at identical positions. The second site of alternative splicing results in the generation of different C termini in dynamin I and in the inclusion or exclusion of an interior four-amino acid sequence in dynamin II. The two dynamins exhibit remarkable differences in their tissue distribution and regulation. Dynamin I is almost exclusively expressed in the central nervous system. Conversely, dynamin II is expressed ubiquitously in all tissues tested. Previous studies revealed that the GTPase activity of dynamin I is regulated by phosphorylation by protein kinase C in nerve terminals. Expression of dynamins I and II by transfection in COS cells demonstrates that only dynamin I but not dynamin II is a substrate for protein kinase C. Our data suggest a specialization in the endocytic functions and the regulation of dynamins between neural and non-neural tissues in mammals.
发动蛋白是一种结合鸟苷三磷酸（GTP）、微管和磷脂的蛋白质，主要在大脑中表达。在果蝇中，发动蛋白基因（shibire基因）编码发动蛋白的一个同源物；该基因的突变导致内吞作用缺陷，提示发动蛋白在内吞膜运输中发挥作用。在本研究中，我们表明哺乳动物中至少有两个不同的发动蛋白基因，其产物分别称为发动蛋白I和发动蛋白II。这两种发动蛋白彼此相似（79%的同一性），并且与果蝇发动蛋白基因产物的同源性相同（66%的同一性）。发动蛋白之间的最高同一性程度出现在它们的N端一半，而它们的C端同源性很小。两种发动蛋白基因的转录本都经历至少两种可变剪接事件，其中第一种在两种发动蛋白中都相同地出现，而第二种可变剪接位点在两种类型的发动蛋白之间是不同的。发动蛋白的第一个可变剪接序列由一个内部区域组成，该区域在两种发动蛋白中以两种不同但同源的形式存在，提示两个基因在相同位置的外显子有交替使用。第二种可变剪接位点导致发动蛋白I产生不同的C端，并导致发动蛋白II中一个内部四氨基酸序列的包含或排除。这两种发动蛋白在组织分布和调节方面表现出显著差异。发动蛋白I几乎只在中枢神经系统中表达。相反，发动蛋白II在所有测试组织中普遍表达。先前的研究表明，发动蛋白I的GTP酶活性在神经末梢受蛋白激酶C磷酸化调节。通过在COS细胞中转染来表达发动蛋白I和发动蛋白II表明，只有发动蛋白I而不是发动蛋白II是蛋白激酶C的底物。我们的数据提示在哺乳动物的神经组织和非神经组织之间，发动蛋白在内吞功能和调节方面存在特化。
