The relevance of the phosphatidylinositolphosphat-binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy
The relevance of the phosphatidylinositolphosphat-binding motif FRRGT of Atg18 and Atg21 for the Cvt pathway and autophagy
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DOI：
10.1016/j.febslet.2006.07.041
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发表时间：
2006-08-21
期刊：
影响因子：
3.5
通讯作者：
Thumm, Michael
中科院分区：
文献类型：
--
作者：
Krick, Roswitha;Tolstrup, Joern;Thumm, Michael
Atg 18和Atg 21是同源的S.自噬蛋白。Atg 18是Cvt囊泡和自噬体的生物发生所必需的，而Atg 21仅是Cvt囊泡形成所必需的。我们发现，突变的Atg 18-（FTTGT）几乎完全失去了与PtdIns 3 P和PtdIns（3，5）P-2的结合，在Cvt途径中无功能，但在自噬和pexophagy中有活性。由于Cvt途径不依赖于PtdIns（3，5）P-2，我们得出结论，Cvt途径需要Atg 18与PtdIns 3 P结合。突变的Atg 21-（FTTGT）在Cvt途径期间是无活性的，但仅显示与PtdIns-磷酸盐的结合部分减少，这表明Atg 21中还有脂质结合结构域。GFP-Atg 18-（FTTGT）和Atg 21-（FTTGT）-GFP从液泡点释放到胞质溶胶。(c)2006年欧洲生物化学学会联合会。Elsevier B. V.出版，保留所有权利。
Atg18 and Atg21 are homologous S. cerevisiae autophagy proteins. Atg18 is essential for biogenesis of Cvt vesicles and autophagosomes, while Atg21 is only essential for Cvt vesicle formation. We found that mutated Atg18-(FTTGT), which lost almost completely its binding to PtdIns3P and PtdIns(3,5)P-2, is non-functional during the Cvt pathway but active during autophagy and pexophagy. Since the Cvt pathway does not depend on PtdIns(3,5)P-2, we conclude that the Cvt pathway requires binding of Atg18 to PtdIns3P. Mutated Atg21-(FTTGT) is inactive during the Cvt pathway but showed only partly reduced binding to PtdIns-phosphates, suggesting further lipid binding domains in Atg21. GFP-Atg18-(FTTGT) and Atg21-(FTTGT)-GFP are released from vacuolar punctae to the cytosol. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.