Редактирование: ATG16L1

Autophagy-related protein 16-1 (APG16-like 1) [APG16L] [UNQ9393/PRO34307]

==Publications==

{{medline-entry
|title=The [[ATG5]]-binding and coiled coil domains of [[ATG16L1]] maintain autophagy and tissue homeostasis in mice independently of the WD domain required for LC3-associated phagocytosis.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/30403914
|abstract=Macroautophagy/autophagy delivers damaged proteins and organelles to lysosomes for degradation, and plays important roles in maintaining tissue homeostasis by reducing tissue damage. The translocation of LC3 to the limiting membrane of the phagophore, the precursor to the autophagosome, during autophagy provides a binding site for autophagy cargoes, and facilitates fusion with lysosomes. An autophagy-related pathway called LC3-associated phagocytosis (LAP) targets LC3 to phagosome and endosome membranes during uptake of bacterial and fungal pathogens, and targets LC3 to swollen endosomes containing particulate material or apoptotic cells. We have investigated the roles played by autophagy and LAP in vivo by exploiting the observation that the WD domain of [[ATG16L1]] is required for LAP, but not autophagy. Mice lacking the linker and WD domains, activate autophagy, but are deficient in LAP. The LAP  mice survive postnatal starvation, grow at the same rate as littermate controls, and are fertile. The liver, kidney, brain and muscle of these mice maintain levels of autophagy cargoes such as LC3 and [[SQSTM1]]/p62 similar to littermate controls, and prevent accumulation of [[SQSTM1]] inclusions and tissue damage associated with loss of autophagy. The results suggest that autophagy maintains tissue homeostasis in mice independently of LC3-associated phagocytosis. Further deletion of glutamate E230 in the coiled-coil domain required for [[WIPI2]] binding produced mice with defective autophagy that survived neonatal starvation. Analysis of brain lysates suggested that interactions between [[WIPI2]] and [[ATG16L1]] were less critical for autophagy in the brain, which may allow a low level of autophagy to overcome neonatal lethality. Abbreviations: CCD: coiled-coil domain; CYBB/NOX2: cytochrome b-245: beta polypeptide; GPT/ALT: glutamic pyruvic transaminase: soluble; LAP: LC3-associated phagocytosis; LC3: microtubule-associated protein 1 light chain 3; MEF: mouse embryonic fibroblast; NOD: nucleotide-binding oligomerization domain; NADPH: nicotinamide adenine dinucleotide phosphate; RUBCN/Rubicon: RUN domain and cysteine-rich domain containing Beclin 1-interacting protein; SLE: systemic lupus erythematosus; [[SQSTM1]]/p62: sequestosome 1; TLR: toll-like receptor; TMEM: transmembrane protein; TRIM: tripartite motif-containing protein; UVRAG: UV radiation resistance associated gene; WD: tryptophan-aspartic acid; WIPI: WD 40 repeat domain: phosphoinositide interacting.
|mesh-terms=* Animals
* Autophagy
* Autophagy-Related Protein 5
* Autophagy-Related Proteins
* Brain
* Carrier Proteins
* Cytokines
* Female
* Fibroblasts
* Homeostasis
* Kidney
* Liver
* Longevity
* Macrophages
* Male
* Mice
* Mice, Inbred C57BL
* Mice, Transgenic
* Microtubule-Associated Proteins
* Muscles
* Phagocytosis
* Phagosomes
* WD40 Repeats
|keywords=* ATG16L1
* LC3-associated phagocytosis
* WD domain
* WIPI2
* brain
* sequestosome 1/p62 inclusions
* tissue homeostasis
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6526875
}}