Meiling-Wesse Khuyen, Epple Ulrike D, Krick Roswitha, Barth Henning, Appelles Anika, Voss Christiane, Eskelinen Eeva-Liisa, Thumm Michael
Center of Biochemistry and Molecular Cell Biology, Georg-August-University, Heinrich-Dueker-Weg 12, D-37073 Goettingen, Germany.
J Biol Chem. 2005 Sep 30;280(39):33669-78. doi: 10.1074/jbc.M501701200. Epub 2005 Aug 3.
Autophagosomes and Cvt vesicles are limited by two membrane layers. The biogenesis of these unconventional vesicles and the origin of their membranes are hardly understood. Here we identify in Saccharomyces cerevisiae Trs85, a nonessential component of the TRAPP complexes, to be required for the biogenesis of Cvt vesicles. The TRAPP complexes function in endoplasmic reticulum-to-Golgi and Golgi trafficking. Growing trs85delta cells show a defect in the organization of the preautophagosomal structure. Although proaminopeptidase I is normally recruited to the preautophagosomal structure, the recruitment of green fluorescent protein-Atg8 depends on Trs85. Autophagy proceeds in the absence of Trs85, albeit at a reduced rate. Our electron microscopic analysis demonstrated that the reduced autophagic rate of trs85delta cells does not result from a reduced size of the autophagosomes. Growing and starved cells lacking Trs85 did not show defects in vacuolar biogenesis; mature vacuolar proteinase B and carboxypeptidase Y were present. Also vacuolar acidification was normal in these cells. It is known that mutations impairing the integrity of the ER or Golgi block both autophagy and the Cvt pathway. But the phenotypes of trs85delta cells show striking differences to those seen in mutants with defects in the early secretory pathway. This suggests that Trs85 might play a direct role in the Cvt pathway and autophagy.
自噬体和Cvt小泡由两层膜界定。这些非常规小泡的生物发生及其膜的来源几乎不为人所知。在这里,我们在酿酒酵母中鉴定出TRAPP复合体的一个非必需成分Trs85,它是Cvt小泡生物发生所必需的。TRAPP复合体在内质网到高尔基体以及高尔基体运输中发挥作用。生长中的trs85Δ细胞在自噬前体结构的组织上存在缺陷。尽管前氨肽酶I通常被招募到自噬前体结构中,但绿色荧光蛋白-Atg8的招募依赖于Trs85。在没有Trs85的情况下自噬仍会进行,尽管速率会降低。我们的电子显微镜分析表明,trs85Δ细胞自噬速率降低并非由于自噬体尺寸减小所致。缺乏Trs85的生长细胞和饥饿细胞在液泡生物发生方面没有表现出缺陷;成熟的液泡蛋白酶B和羧肽酶Y存在。这些细胞中的液泡酸化也正常。已知损害内质网或高尔基体完整性的突变会阻断自噬和Cvt途径。但trs85Δ细胞的表型与早期分泌途径有缺陷的突变体所表现出的表型有显著差异。这表明Trs85可能在Cvt途径和自噬中发挥直接作用。