When the autophagy protein ATG16L1 met the ciliary protein IFT20. Issue 7 (3rd July 2021)

• Record Type: Journal Article
• Authors: Boukhalfa, Asma; Roccio, Federica; Dupont, Nicolas; Codogno, Patrice; Morel, Etienne
• Is Part Of: Autophagy. Volume 17:Issue 7(2021)
• Page Start: 1791
• Page End: 1793
• Publication Date: 2021-07-03
• Subjects: ATG -- IFT -- INPP5E -- macroautophagy -- phosphoinositides -- primary cilium; Autophagic vacuoles -- Periodicals; Apoptosis -- Periodicals; Cell death -- Periodicals; Lysosomes -- Periodicals; Degeneration (Pathology) -- Periodicals; Autophagy -- Periodicals; Cell Death -- Periodicals; Lysosomes -- Periodicals; Periodicals; 571.936
• DOI: 10.1080/15548627.2021.1935004
• Languages: English
• ISSNs: 1554-8627

Abstract

ABSTRACT: The primary cilium (PC), a plasma membrane microtubule-based structure, is a sensor of extracellular chemical and mechanical stress stimuli. Upon ciliogenesis, the autophagy protein ATG16L1 and the ciliary protein IFT20 are co-transported to the PC. We demonstrated in a recent study that IFT20 and ATG16L1 interact in a multiprotein complex. This interaction is mediated by the ATG16L1 WD40 domain and an ATG16L1-binding motif newly identified in IFT20. ATG16L1-deficient cells are decorated by giant ciliary structures hallmarked by defects in PC-associated signaling. These structures uncommonly accumulate phosphatidylinositol-4, 5-bisphosphate (PtdIns[4, 5]P2 ) while phosphatidylinositol-4-phosphate (PtdIns4P), a lipid normally concentrated in the PC, is excluded. We show that INPP5E, a phosphoinositide-associated phosphatase responsible for PtdIns4P generation, is a partner of ATG16L1 in this context. Perturbation of the ATG16L1-IFT20 complex alters INPP5E trafficking and proper function at the ciliary membrane. Altogether, these results reveal a novel autophagy-independent function of ATG16L1 that contributes to proper PC dynamics and function.