Autophagy initiation triggers p150 Glued -AP-2β interaction on the lysosomes and facilitates their transport.

Autor: Tempes A; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Bogusz K; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Brzozowska A; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Weslawski J; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Macias M; Microscopy and Flow Cytometry Core Facility, International Institute of Molecular and Cell Biology, Warsaw, Poland., Tkaczyk O; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Orzoł K; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Lew A; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Calka-Kresa M; Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland., Bernas T; Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland.; Microscopy Facility, Department of Anatomy and Neurology, Virginia Commonwealth University School of Medicine, Richmond, VA, USA., Szczepankiewicz AA; Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland., Mlostek M; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Kumari S; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Liszewska E; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Machnicka K; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland., Bakun M; Institute of Biochemistry and Biophysics, Polish Academy of Sciences, Warsaw, Poland., Rubel T; Institute of Radioelectronics and Multimedia Technology, Warsaw University of Technology, Warsaw, Poland., Malik AR; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland. ar.malik@uw.edu.pl.; Cellular Neurobiology Research Group, Institute of Developmental Biology and Biomedical Sciences, Faculty of Biology, University of Warsaw, Miecznikowa St. 1, 02-096, Warsaw, Poland. ar.malik@uw.edu.pl., Jaworski J; Laboratory of Molecular and Cellular Neurobiology, International Institute of Molecular and Cell Biology, Ks. Trojdena St. 4, 02-109, Warsaw, Poland. jaworski@iimcb.gov.pl.
Jazyk: angličtina
Zdroj: Cellular and molecular life sciences : CMLS [Cell Mol Life Sci] 2024 May 17; Vol. 81 (1), pp. 218. Date of Electronic Publication: 2024 May 17.
DOI: 10.1007/s00018-024-05256-6
Abstrakt: The endocytic adaptor protein 2 (AP-2) complex binds dynactin as part of its noncanonical function, which is necessary for dynein-driven autophagosome transport along microtubules in neuronal axons. The absence of this AP-2-dependent transport causes neuronal morphology simplification and neurodegeneration. The mechanisms that lead to formation of the AP-2-dynactin complex have not been studied to date. However, the inhibition of mammalian/mechanistic target of rapamycin complex 1 (mTORC1) enhances the transport of newly formed autophagosomes by influencing the biogenesis and protein interactions of Rab-interacting lysosomal protein (RILP), another dynein cargo adaptor. We tested effects of mTORC1 inhibition on interactions between the AP-2 and dynactin complexes, with a focus on their two essential subunits, AP-2β and p150 Glued . We found that the mTORC1 inhibitor rapamycin enhanced p150 Glued -AP-2β complex formation in both neurons and non-neuronal cells. Additional analysis revealed that the p150 Glued -AP-2β interaction was indirect and required integrity of the dynactin complex. In non-neuronal cells rapamycin-driven enhancement of the p150 Glued -AP-2β interaction also required the presence of cytoplasmic linker protein 170 (CLIP-170), the activation of autophagy, and an undisturbed endolysosomal system. The rapamycin-dependent p150 Glued -AP-2β interaction occurred on lysosomal-associated membrane protein 1 (Lamp-1)-positive organelles but without the need for autolysosome formation. Rapamycin treatment also increased the acidification and number of acidic organelles and increased speed of the long-distance retrograde movement of Lamp-1-positive organelles. Altogether, our results indicate that autophagy regulates the p150 Glued -AP-2β interaction, possibly to coordinate sufficient motor-adaptor complex availability for effective lysosome transport.
(© 2024. The Author(s).)
Databáze: MEDLINE
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