【摘 要】
：
Autophagy requires the Vps34-containing phosphatidylinositol 3-kinase (PI3K).Vps34 exists in two distinct complexes: PI3K complex Ⅰ and PI3K complex Ⅱ.The
【机 构】
：
NationalInstituteofBiologicalSciences,Beijing,China
【出 处】
：
The 7th International Symposium on Autophagy 2015(第七届自噬国际研讨会
论文部分内容阅读
Autophagy requires the Vps34-containing phosphatidylinositol 3-kinase (PI3K).Vps34 exists in two distinct complexes: PI3K complex Ⅰ and PI3K complex Ⅱ.The former, consisting of Vps34,Vps15, Atg6Nps30 and Atg14, functions in autophagy;and the latter, composed of Vps34,Vps15, Atg6Nps30 and Vps38, participates in vacuolar protein sorting.Recent reports suggest that complex Ⅰ harbors one additional subunit, called Atg38 in budding yeast and NRBF2 in mammals, but their exact roles are not entirely clear.Through parallel efforts of genetic screening and protein complex purification, we identified a new autophagy gene in the fission yeast Schizosaccharomyces pombe and found that it encodes a new subunit of PI3K complex I.This protein contains a N-terminal MIT domain and a C-terminal coiled-coil domain, and thus resembles budding yeast Atg38 and mammalian NRBF2 in domain organization.We named it Atg38.Upon starvation treatment, Atg38 localizes to the pre-autophagosomal structure (PAS),and this localization is dependent on Atg14.Atg38 seems to be dispensable for the interactions between other complex I subunits, but in its absence, the PAS localization of Atg14 is significantly weakened.Reducing the expression level of Atg14 resulted in phenotypes similar to those of atg38 deletion mutant.Furthermore, fusing Atg14 and Atg13 together partially rescues the autophagy defect of atg38 deletion.We propose that Atg38 promotes starvation-induced autophagy by enhancing the PAS localization of PI3K complex Ⅰ.
其他文献
Tumor hypoxia underlies treatment failure and yields more aggressive and metastatic cancer phenotypes.Although therapeutically targeting these hypoxic envir
Autophagy is a dynamic process accomplished by the generation and maturation of autophagosomes.Isolation of autophagosomes and subsequent compositional anal
Lysosomes are dynamic organelles involved in cellular clearance processes.It has been suggested that chronic impairment of cellular clearance may be a major
EHMT2/G9a (euchromatic histone-lysine N-methyltransferase 2;EHMT2) is highly expressed in various human cancers, including aggressive breast cancer, prostat
Excess mitochondrial stress and/or mitochondrial dysfunction are implicated in the development of neurodegenerative disease such as Parkinson's disease.Dama
We and multiple collaborators have begun to analyze the role of autophagy-related genes in mice infected with Toxoplasma gondii, Mycobacterium tuberculosis (M.t
Lysosomes are specialized membrane bound organelles that degrade macromolecular cargoes derived from endocytosis, phagocytosis or autophagy.The resulting catabo
The class Ⅲ phosphatidylinositol 3-kinase complex Ⅰ (PI3KC3-C1) that functions in early autophagy consists of the lipid kinase VPS34, the scaffolding prot
Caveolin-1 (CAV1) is well known as a principle scaffolding protein of caveolae, a specialized plasma membrane structure.Relatively the caveolae-independent