Degradation of p0071 and p120-catenin during adherens junction disassembly by Leptospira interrogans .

Autor:	Tokumon R; Department of Bacteriology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan., Sebastián I; Department of Bacteriology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan., Humbel BM; Provost Office, Okinawa Institute of Science and Technology Graduate University, Okinawa, Japan.; Microscopy Center, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil.; Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan., Okura N; Department of Molecular Anatomy, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan., Yamanaka H; Environmental Technology Department, Chemicals Evaluation and Research Institute, Saitama, Japan., Yamashiro T; Department of Bacteriology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan., Toma C; Department of Bacteriology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
Jazyk:	angličtina
Zdroj:	Frontiers in cellular and infection microbiology [Front Cell Infect Microbiol] 2023 Sep 15; Vol. 13, pp. 1228051. Date of Electronic Publication: 2023 Sep 15 (Print Publication: 2023).
DOI:	10.3389/fcimb.2023.1228051
Abstrakt:	Leptospira interrogans disseminates hematogenously to reach the target organs by disrupting epithelial adherens junctions (AJs), thus causing leptospirosis, which is a globally neglected zoonotic disease. L. interrogans induces E-cadherin (E-cad) endocytosis and cytoskeletal rearrangement during AJ disassembly, but the detailed mechanism remains unknown. Elucidation of AJ disassembly mechanisms will guide new approaches to developing vaccines and diagnostic methods. In this study, we combine proteomic and imaging analysis with chemical inhibition studies to demonstrate that disrupting the AJs of renal proximal tubule epithelial cells involves the degradation of two armadillo repeat-containing proteins, p0071 and p120-catenin, that stabilize E-cad at the plasma membrane. Combining proteasomal and lysosomal inhibitors substantially prevented p120-catenin degradation, and monolayer integrity destruction without preventing p0071 proteolysis. In contrast, the pan-caspase inhibitor Z-VAD-FMK inhibited p0071 proteolysis and displacement of both armadillo repeat-containing proteins from the cell-cell junctions. Our results show that L. interrogans induces p120-catenin and p0071 degradation, which mutually regulates E-cad stability by co-opting multiple cellular degradation pathways. This strategy may allow L. interrogans to disassemble AJs and disseminate through the body efficiently. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Tokumon, Sebastián, Humbel, Okura, Yamanaka, Yamashiro and Toma.)
Databáze:	MEDLINE
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