title: Dissecting the involvement of LC3B and GATE-16 in p62 recruitment into autophagosomes.
abstract: Autophagy is a major intracellular trafficking pathway that delivers proteins and organelles from the cytoplasm into lysosomes for consequential degradation and recycling. Mammalian Atg8s are key autophagic factors that undergo a unique ubiquitin-like conjugation to the lipid phase of the autophagosomal membrane. In addition to their activity in autophagosome formation, several Atg8s directly bind p62/SQSTM1. Here we show that LC3 and GATE-16 differ in their mode of p62 binding. While the soluble form of both LC3 and GATE-16 bind p62, only the lipidated form of LC3 is directly involved in p62 recruitment into autophagosomes. Moreover, by utilizing chimeras of LC3 and GATE-16 where their N-terminus was swapped, we determined the regions responsible for this differential binding. Accordingly, we found that the chimera of GATE-16 containing the LC3 N-terminal region acts similarly to wild-type LC3 in recruiting p62 into autophagosomes. We therefore propose that LC3 is responsible for the final stages of p62 incorporation into autophagosomes, a process selectively mediated by its N-terminus.
authors: Department of Biological Chemistry, The Weizmann Institute of Science, Rehovot, Israel. zvulun.elazar@weizmann.ac.il
authors: Elena
authors: E
authors: Shvets
authors: Adi
authors: A
authors: Abada
authors: Hilla
authors: H
authors: Weidberg
authors: Zvulun
authors: Z
authors: Elazar
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D001343:Autophagy; D006367:HeLa Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D011485:Protein Binding; D000071456:Sequestosome-1 Protein; D013329:Structure-Activity Relationship
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; C099718:SQSTM1 protein, human; D000071456:Sequestosome-1 Protein