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. 2021 Dec 29;18(9):2086–2103. doi: 10.1080/15548627.2021.2016233

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Figure 11. — Schematic model of autophagy-induced CLDN2/Claudin-2 degradation. Autophagy and AAK1 (AP2 associated kinase 1) activates AP2/Adaptor protein-2 via phosphorylation of AP2M1 (adaptor related protein complex 2 subunit mu 1). Activated AP2M1 binds to YXXΦ (AP2M1 binding site) region of CLDN2 and facilitate its CLTC/clathrin-mediated endocytosis. AP2 also contains LC3 interacting region and acts as a bridge in connecting endocytosed CLDN2 to LC3. ATG7 dependent LC3 lipidation is required for internalization of CLDN2 into autophagosomes. The CLDN2-containing autophagosome fuses with lysosome, resulting in degradation of CLDN2.