Urrutia R, Henley J R, Cook T, McNiven M A
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN 55905, USA.
Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):377-84. doi: 10.1073/pnas.94.2.377.
In the 7 years since dynamin was first isolated from bovine brain in search of novel microtubule-based motors, our understanding of this enzyme has expanded significantly. We now know that brain dynamin belongs to a family of large GTPases, which mediate vesicle trafficking. Furthermore, this enzymatic activity is markedly increased through association with microtubules, acidic phospholipids, and certain regulatory proteins that contain Src homology 3 (SH3) domains. From functional, genetic, and cellular manipulations, it is now generally accepted that dynamin participates in the endocytic uptake of receptors, associated ligands, and plasma membrane following an exocytic event. These observations have confirmed at least one function of dynamin that was predicted from seminal studies on a pleiotropic mutant, shibire(ts) (shi(ts)) in Drosophila melanogaster. Of equal interest is the finding that there are multiple dynamin gene products, including two that are expressed in a tissue-specific manner, and they share marked homology with a larger family of distinct but related proteins. Therefore, it is attractive to speculate that the different dynamins may participate in related cellular functions, such as distinct endocytic processes and even secretion. In turn, dynamin could play an important role in cell growth, cell spreading, and neurite outgrowth. The purpose of this review is to enumerate on the expansive dynamin literature and to discuss the nomenclature, expression, and putative functions of this growing and interesting family of proteins.
自从为寻找新型基于微管的马达蛋白而首次从牛脑中分离出发动蛋白以来的7年里,我们对这种酶的理解有了显著扩展。我们现在知道,脑发动蛋白属于一个大GTP酶家族,该家族介导囊泡运输。此外,通过与微管、酸性磷脂以及某些含有Src同源3(SH3)结构域的调节蛋白结合,这种酶活性会显著增加。从功能、遗传和细胞操作方面来看,现在普遍认为发动蛋白在胞吐事件后参与受体、相关配体和质膜的内吞摄取。这些观察结果证实了发动蛋白的至少一项功能,这一功能是从对果蝇中一种多效性突变体——失活(温度敏感型)(shi(ts))的开创性研究中预测出来的。同样有趣的是,发现有多种发动蛋白基因产物,包括两种以组织特异性方式表达的产物,它们与一个更大的不同但相关的蛋白质家族有显著的同源性。因此,推测不同的发动蛋白可能参与相关的细胞功能,如不同的内吞过程甚至分泌,是很有吸引力的。反过来,发动蛋白可能在细胞生长、细胞铺展和神经突生长中发挥重要作用。这篇综述的目的是梳理关于发动蛋白的大量文献,并讨论这个不断发展且有趣的蛋白质家族的命名、表达和假定功能。