Wigge P, McMahon H T
Neurobiology Division, MRC Laboratory of Molecular Biology, Cambridge, UK.
Trends Neurosci. 1998 Aug;21(8):339-44. doi: 10.1016/s0166-2236(98)01264-8.
Clathrin-mediated endocytosis at the plasma membrane is a major pathway of synaptic vesicle recycling in neurones, but little is known about the molecular machinery that orchestrates the process. The amphiphysin protein has recently emerged into the limelight since its discovery in 1992 as a synaptic vesicle-associated protein. It was subsequently found to interact in vitro with the GTPase dynamin through its SH3 domain. However, only in the past year has its role in endocytosis been confirmed, with the demonstration that the introduction of dominant-negative-acting SH3 domains into living cells causes a potent blockade of clathrin-mediated endocytosis. This, together with the discovery by several groups of a second nerve terminal-enriched amphiphysin isoform, and the finding that the two proteins heterodimerize, further suggests that the amphiphysins are closely connected with dynamin-mediated vesicle budding. This review summarizes current views in the field, and draws on data that suggest intriguing alternative roles--including possible involvement in the cytoskeleton and in tumour suppression--for certain members of the amphiphysin family.
网格蛋白介导的质膜内吞作用是神经元中突触小泡循环利用的主要途径，但对于协调这一过程的分子机制却知之甚少。自1992年被发现作为一种与突触小泡相关的蛋白以来，发动蛋白就备受关注。随后发现它通过其SH3结构域在体外与GTP酶发动蛋白相互作用。然而，直到去年其在内吞作用中的作用才得到证实，有研究表明将显性负性作用的SH3结构域导入活细胞会导致网格蛋白介导的内吞作用受到有效阻断。这一点，再加上几组研究人员发现了第二种在神经末梢富集的发动蛋白异构体，以及这两种蛋白能形成异源二聚体的发现，进一步表明发动蛋白与发动蛋白介导的小泡出芽密切相关。这篇综述总结了该领域的当前观点，并借鉴了一些数据，这些数据表明发动蛋白家族的某些成员具有有趣的其他作用，包括可能参与细胞骨架和肿瘤抑制。
