title: WIPI2b and Atg16L1: setting the stage for autophagosome formation.
abstract: The double-membraned autophagosome organelle is an integral part of autophagy, a process that recycles cellular components by non-selectively engulfing and delivering them to lysosomes where they are digested. Release of metabolites from this process is involved in cellular energy homoeostasis under basal conditions and during nutrient starvation. Selective engulfment of protein aggregates and dysfunctional organelles by autophagosomes also prevents disruption of cellular metabolism. Autophagosome formation in animals is crucially dependent on the unique conjugation of a group of ubiquitin-like proteins in the microtubule-associated proteins 1A/1B light chain 3 (LC3) family to the headgroup of phosphatidylethanolamine (PE) lipids. LC3 lipidation requires a cascade of ubiquitin-like ligase and conjugation enzymes. The present review describes recent progress and discovery of the direct interaction between the PtdIns3P effector WIPI2b and autophagy-related protein 16-like 1 (Atg16L1), a component of the LC3-conjugation complex. This interaction makes the link between endoplasmic reticulum (ER)-localized production of PtdIns3P, triggered by the autophagy regulatory network, and recruitment of the LC3-conjugation complex crucial for autophagosome formation.
authors.affiliation: *The Babraham Institute, Babraham Research Campus, Cambridge CB22 3AT, U.K.
authors.forename: Michael I
authors.initials: MI
authors.lastname: Wilson
authors.affiliation: †London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, U.K.
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Dooley
authors.affiliation: †London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3LY, U.K.
authors.forename: Sharon A
authors.initials: SA
authors.lastname: Tooze
mesh_terms: D000818:Animals; D001343:Autophagy; D000071183:Autophagy-Related Proteins; D001665:Binding Sites; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D019281:Dimerization; D006801:Humans; D007425:Intracellular Membranes / Q000737:chemistry / Q000378:metabolism; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D010588:Phagosomes / Q000378:metabolism*; D028044:Phosphate-Binding Proteins; D018129:Phosphatidylinositol Phosphates / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs
chemical_list: C518959:ATG16L1 protein, human; D000071183:Autophagy-Related Proteins; D002352:Carrier Proteins; D008565:Membrane Proteins; D028044:Phosphate-Binding Proteins; D018129:Phosphatidylinositol Phosphates; C569007:WIPI2 protein, human; C055525:phosphatidylinositol 3-phosphate