Roles of Pichia pastoris Uvrag in vacuolar protein sorting and the phosphatidylinositol 3-kinase complex in phagophore elongation in autophagy pathways.

Roles of Pichia pastoris Uvrag in vacuolar protein sorting and the phosphatidylinositol 3-kinase complex in phagophore elongation in autophagy pathways.
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DOI:
10.4161/auto.6.1.10535
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发表时间:
2010-01
期刊:
影响因子:
13.3
通讯作者:
Subramani S
Subramani S
中科院分区:
生物学1区
文献类型:
--
作者:
Farré JC;Mathewson RD;Manjithaya R;Subramani S

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尽管已经确定 Atg6/Beclin 1、磷脂酰肌醇 3 激酶 (PI3K) Vps34 和相关蛋白在哺乳动物和酵母的自噬途径中具有直接或间接作用,但对这些作用及其所需蛋白的阐明仍在继续。 Beclin 1 结合蛋白 UVRAG 的参与一直是争论的一个特殊根源。我们发现 PpAtg6 是酵母毕赤酵母中已鉴定的所有自噬途径以及羧肽酶 Y (PpCPY) 液泡蛋白分选途径所必需的。我们将 PpAtg6 定位于吞噬细胞组装位点 (PAS),并观察到随着隔离膜从其生长并成熟为 pexophagosome,它在该位点持续存在。然而,PpUvrag 是正确的 PpCPY 分选所必需的,但不是任何自噬途径所必需的。相反,当 PpUvrag 过表达时观察到的所有自噬途径中的缺陷支持其存在于与自噬所需的 PI3K 复合物竞争的复合物中。
Although it has been established that Atg6/Beclin 1, the phosphatidylinositol 3-kinase (PI3K) Vps34, and associated proteins have direct or indirect roles in autophagic pathways in both mammals and yeasts, the elucidation of these roles and the proteins required for them is ongoing. The involvement of the Beclin 1-binding protein, UVRAG, has been a particular source of disagreement. We found that PpAtg6 is required for all autophagic pathways that have been identified in the yeast Pichia pastoris, as well as for the carboxypeptidase Y (PpCPY) vacuolar protein sorting pathway. We localized PpAtg6 to the phagophore assembly site (PAS) and observed its continued presence at that site as the isolation membrane grew from it and matured into a pexophagosome. PpUvrag, however, was required for proper PpCPY sorting, but not for any autophagic pathway. Rather, the defects in all autophagic pathways observed when PpUvrag was overexpressed support its presence in a complex that competes with the PI3K complex required for autophagy.
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