自噬
生物
自噬相关蛋白13
袋3
细胞生物学
蛋白激酶A
磷酸化
蛋白质亚单位
ULK1
生物化学
液泡
激酶
蛋白激酶结构域
丝裂原活化蛋白激酶激酶
细胞质
突变体
安普克
基因
细胞凋亡
作者
Weijing Yao,Yixing Li,Yingcong Chen,Yuting Chen,Yu Xie,Miaojuan Ye,Ying Zhang,Xiangjun Chen,Xiaoyong Wu,Yuyao Feng,Zhi Hong,Yigang Wang,Wei Liu,Cong Yi
出处
期刊:Autophagy
[Informa]
日期:2022-04-15
卷期号:19 (1): 180-188
被引量:5
标识
DOI:10.1080/15548627.2022.2063494
摘要
Atg11 is an adaptor protein required for the induction of selective autophagy via receptor binding. However, our understanding of the molecular mechanisms by which it regulates selective autophagy remains incomplete. Here, we show that Atg11 is phosphorylated by Atg1. Rapamycin treatment or starvation conditions induced slower electrophoretic mobility of Atg11 in an Atg1 kinase activity-dependent manner. Through in vitro kinase assays combined with mutagenesis, we determined that Atg1 phosphorylates S949, S1057, and S1064 residues in CC4 domain of Atg11. Replacing the three residues with alanine suppressed the cleavage of selective autophagy substrates for the cytoplasm-to-vacuole targeting (Cvt) pathway, mitophagy, reticulophagy, and pexophagy. The Atg11 mutant was defective in binding to related selective autophagy receptors. These results demonstrate a previously unknown function of Atg1 in regulation of selective autophagy via Atg11 phosphorylation.Abbreviations: AMPK: AMP-activated protein kinase; ATG: autophagy-related; Cvt: cytoplasm-to-vacuole targeting; FUNDC1: FUN14 domain-containing protein 1; GFP: green fluorescent protein; MTOR: mechanistic target of rapamycin kinase; PAS: phagophore assembly site; PIK3C3: phosphatidylinositol 3-kinase catalytic subunit type 3; PRKAC/PKA: protein kinase cAMP-activated; SD-G: glucose starvation; SD-N: nitrogen starvation; ULK1: unc-51 like autophagy activating kinase 1; λ-PPase: lambda protein phosphatase.
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