Membrane dynamics of ATG4B and LC3 in autophagosome formation
作者机构：Key Laboratory of Regenerative Medicine of Ministry of EducationGuangzhou Regenerative Medicine and Health Guangdong LaboratoryInstitute of Aging and Regenerative MedicineJinan UniversityGuangzhou 510632China Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing)Department of Bone and Soft Tissue TumorPeking University Cancer Hospital and InstituteBeijing 100142China College of BioengineeringHangzhou Medical CollegeHangzhou 310013China
出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)
年 卷 期：2021年第13卷第12期
页 面：853-863页
核心收录：
学科分类：0710[理学-生物学] 07[理学] 071009[理学-细胞生物学]
基 金：the National Natural Science Foundation of China(31671434,31701203,81420108017,81525010,and 91749203) the National Key Research and Development Program of China(2016YFA0100602,2017YFA0103302,2020YFA0112404,and 2018YFC2000705) the Program for Guangdong Introducing Innovative and Entrepreneurial Teams(2017ZT07S347) the Fundamental Research Funds for the Central Universities(21617336).
主 题：autophagy autophagosome biogenesis ATG4 LC3 live-cell imaging membrane binding kinetics
摘 要：The biogenesis of autophagosomes provides the basis for macroautophagy to capture and degrade intracellular cargoes.Binding of the autophagy-related protein ATG8/LC3 to autophagic membranes is essential to autophagosome formation,which involves the specific and dynamic processing of ATG8/LC3 by cysteine protease ATG4.However,to date,the mechanism whereby ATG4 is recruited to the membranes,the interaction of ATG4 and ATG8/LC3 on the membranes,and its role in the growth of phagophore are not completely understood.Here,we used fluorescence recovery after photobleaching to monitor the turnover of GFP-tagged ATG4B and LC3B in living animal cells.The data show that ATG4B localizes to early autophagic membranes in an LC3B-dependent manner.During autophagy,ATG4B and LC3B undergo rapid cytosol/isolation membrane exchange but not at the cytosol/completed autophagosome.In addition,ATG4B activity controls the efficiency of autophagosome formation by impacting the membrane binding/dissociation of LC3B.These data suggest that ATG4 and LC3 play interdependent roles in the formation of autophagosomes.
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