The stimulatory action of amphiphysin on dynamin function is dependent on lipid bilayer curvature
The stimulatory action of amphiphysin on dynamin function is dependent on lipid bilayer curvature
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DOI：
10.1038/sj.emboj.7600355
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发表时间：
2004-09-01
期刊：
影响因子：
11.4
通讯作者：
Takei, K
中科院分区：
文献类型：
--
作者：
Yoshida, Y;Kinuta, M;Takei, K
Amphiphysin是突触上主要的动力蛋白结合伙伴；然而，它在裂变中的作用尚不清楚。大单层脂质体与小鼠脑细胞质孵育导致大量小囊泡的形成，而敲除amphiphysin 1小鼠的细胞质在此反应中效率要低得多。由纯化的动力蛋白产生的大脂质体的囊泡形成也被两性素强烈地促进。在脂质体存在的情况下，amphiphysin强烈影响动力蛋白GTPase活性和动力蛋白向脂质体的募集，但这种活性高度依赖于脂质体的大小。从amphiphysin中删除其中心的富含脯氨酸的延伸显著增强了其对动力蛋白的作用，可能是通过减轻抑制分子内相互作用。这些结果提示了一个模型，在这个模型中，内吞坑的成熟与动力蛋白与两性蛋白或其他具有类似结构域结构的蛋白质的寡聚化有关。这些复合物的形成与动力蛋白GTPase活性的激活相结合，从而解释了深坑内陷导致裂变的原因。
Amphiphysin is a major dynamin-binding partner at the synapse; however, its function in fission is unclear. Incubation of large unilamellar liposomes with mice brain cytosol led to massive formation of small vesicles, whereas cytosol of amphiphysin 1 knockout mice was much less efficient in this reaction. Vesicle formation from large liposomes by purified dynamin was also strongly enhanced by amphiphysin. In the presence of liposomes, amphiphysin strongly affected dynamin GTPase activity and the recruitment of dynamin to the liposomes, but this activity was highly dependent on liposome size. Deletion from amphiphysin of its central proline-rich stretch dramatically potentiated its effect on dynamin, possibly by relieving an inhibitory intramolecular interaction. These results suggest a model in which maturation of endocytic pits correlates with the oligomerization of dynamin with either amphiphysin or other proteins with similar domain structure. Formation of these complexes is coupled to the activation of dynamin GTPase activity, thus explaining how deep invagination of the pit leads to fission.