title: A tethering coherent protein in autophagosome maturation.
abstract: Autophagy is a cellular pathway that degrades damaged organelles, cytosol and microorganisms, thereby maintaining human health by preventing various diseases including cancers, neurodegenerative disorders and diabetes. In autophagy, autophagosomes carrying cellular cargoes fuse with lysosomes for degradation. The proper autophagosome-lysosome fusion is pivotal for efficient autophagy activity. However, the molecular mechanism that specifically directs the fusion process is not clear. Our study reported that lysosome-localized TECPR1 (TECtonin β-Propeller Repeat containing 1) binds the autophagosome-localized ATG12-ATG5 conjugate and recruits it to autolysosomes. TECPR1 also binds PtdIns3P in an ATG12-ATG5-dependent manner. Consequently, depletion of TECPR1 leads to a severe defect in autophagosome maturation. We propose that the interaction between TECPR1 and ATG12-ATG5 initiates the fusion between the autophagosome and lysosome, and TECPR1 is a TEthering Coherent PRotein in autophagosome maturation.
authors.affiliation: Division of Biochemistry, Biophysics and Structural Biology, Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, CA, USA.
authors.forename: Dandan
authors.initials: D
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhong
mesh_terms: D000818:Animals; D001343:Autophagy; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism*; D011485:Protein Binding
chemical_list: D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins