Oku Masahide, Nishimura Taku, Hattori Takeshi, Ano Yoshitaka, Yamashita Shun-ichi, Sakai Yasuyoshi
Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kitashirakawa-Oiwake, Sakyo-ku, Kyoto, Japan.
Autophagy. 2006 Oct-Dec;2(4):272-9. doi: 10.4161/auto.3135. Epub 2006 Oct 30.
Vac8 is a yeast vacuolar membrane protein involved in vacuolar membrane dynamics, e.g., vacuole inheritance and vacuolar membrane fusion. This protein is also necessary for a subset of autophagic pathways that deliver specific cellular components to the vacuole. In this study, we show that the micropexohagy and vacuole inheritance required distinct domain structures of Pichia pastoris Vac8 (PpVac8). Whereas vacuole inheritance required the Armadillo repeat (ARM) region that resides in the middle part of the protein, micropexophagy did not. Deletion of both the ARM and C-terminal domains inhibited a characteristic of vacuolar dynamics during micropexophagy, i.e., formation of the vacuolar sequestering membrane (VSM). Subsequent analyses indicated that PpVAC8 disruption abolished recruitment of PpAtg11, another protein required for formation of the VSM, to the vacuolar membrane. These results present a novel molecular function of PpVac8 in micropexophagy.
Vac8是一种酵母液泡膜蛋白，参与液泡膜动态变化，如液泡遗传和液泡膜融合。该蛋白对于将特定细胞成分输送到液泡的自噬途径子集也是必需的。在本研究中，我们表明微小过氧化物酶体自噬和液泡遗传需要巴斯德毕赤酵母Vac8（PpVac8）的不同结构域。液泡遗传需要位于蛋白质中部的犰狳重复（ARM）区域，而微小过氧化物酶体自噬则不需要。ARM和C末端结构域的缺失抑制了微小过氧化物酶体自噬过程中液泡动态变化的一个特征，即液泡隔离膜（VSM）的形成。随后的分析表明，PpVAC8的破坏消除了另一种VSM形成所需的蛋白质PpAtg11向液泡膜的募集。这些结果揭示了PpVac8在微小过氧化物酶体自噬中的一种新的分子功能。
