Lysosomal Exocytosis: The Extracellular Role of an Intracellular Organelle.
Brunella Tancini,Sandra Buratta,Federica Delo,Krizia Sagini,Elisabetta Chiaradia,Roberto Maria Pellegrino,Carla Emiliani,Lorena Urbanelli +7 more
- Vol. 10, Iss: 12, pp 406
TLDR
Light is shed on the potential of lysosomal exocytosis stimulation as a therapeutic approach to shed light on the current literature on molecular mechanisms and biological functions underlying lysOSomal excytosis.Abstract:
Lysosomes are acidic cell compartments containing a large set of hydrolytic enzymes. These lysosomal hydrolases degrade proteins, lipids, polysaccharides, and nucleic acids into their constituents. Materials to be degraded can reach lysosomes either from inside the cell, by autophagy, or from outside the cell, by different forms of endocytosis. In addition to their degradative functions, lysosomes are also able to extracellularly release their contents by lysosomal exocytosis. These organelles move from the perinuclear region along microtubules towards the proximity of the plasma membrane, then the lysosomal and plasma membrane fuse together via a Ca2+-dependent process. The fusion of the lysosomal membrane with plasma membrane plays an important role in plasma membrane repair, while the secretion of lysosomal content is relevant for the remodelling of extracellular matrix and release of functional substrates. Lysosomal storage disorders (LSDs) and age-related neurodegenerative disorders, such as Parkinson's and Alzheimer's diseases, share as a pathological feature the accumulation of undigested material within organelles of the endolysosomal system. Recent studies suggest that lysosomal exocytosis stimulation may have beneficial effects on the accumulation of these unprocessed aggregates, leading to their extracellular elimination. However, many details of the molecular machinery required for lysosomal exocytosis are only beginning to be unravelled. Here, we are going to review the current literature on molecular mechanisms and biological functions underlying lysosomal exocytosis, to shed light on the potential of lysosomal exocytosis stimulation as a therapeutic approach.read more
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mTOR Signaling in Growth, Metabolism, and Disease
TL;DR: Recent advances in understanding of mTOR function, regulation, and importance in mammalian physiology are reviewed and how the mTOR-signaling network contributes to human disease is highlighted.
Journal ArticleDOI
ORF3a of SARS-CoV-2 promotes lysosomal exocytosis-mediated viral egress.
TL;DR: In this article, the authors showed that SARS-CoV-2 ORF3a, but not SARS CoV ORF 3a, promoted lysosomal exocytosis.
Journal ArticleDOI
Current methods to analyze lysosome morphology, positioning, motility and function
Duarte C. Barral,Leopoldo Staiano,Claudia G. Almeida,Daniel F. Cutler,Emily R. Eden,Clare E. Futter,Antony Galione,André R. A. Marques,Diego L. Medina,Gennaro Napolitano,Carmine Settembre,Otilia V. Vieira,Johannes M. F. G. Aerts,Peace Atakpa-Adaji,Gemma Bruno,Antonella Capuozzo,Elvira De Leonibus,Chiara Di Malta,Cristina Escrevente,Alessandra Esposito,Paolo Grumati,Michael J. Hall,Rita O. Teodoro,Susana S. Lopes,J. Paul Luzio,Jlenia Monfregola,Sandro Montefusco,Frances M. Platt,Roman S. Polishuck,Maria De Risi,Irene Sambri,Chiara Soldati,Miguel C. Seabra +32 more
TL;DR: This review aims to stimulate an increase in the quantity and quality of research on lysosomes and further ground‐breaking discoveries on an organelle that continues to surprise and excite cell biologists.
Journal ArticleDOI
LRRK2 kinase activity regulates GCase level and enzymatic activity differently depending on cell type in Parkinson’s disease
Maria Kedariti,Emanuele Frattini,Pascale Baden,Susanna Cogo,Laura Civiero,Elena Ziviani,Gianluca Zilio,Federico Lorenzo Bertoli,Massimo Aureli,Alice Kaganovich,Mark R. Cookson,Leonidas Stefanis,Matthew Surface,Michela Deleidi,Alessio Di Fonzo,Roy N. Alcalay,Hardy J. Rideout,Elisa Greggio,Nicoletta Plotegher +18 more
TL;DR: In this article , the authors performed a comprehensive analysis of GCase levels and activity in complementary LRRK2 models, including GBA1-linked and idiopathic Parkinson's disease.
Journal ArticleDOI
The role of endolysosomal trafficking in anticancer drug resistance
Noor Hussein,Saloni Malla,Mariah A. Pasternak,David Terrero,Noah G. Brown,Charles R. Ashby,Yehuda G. Assaraf,Zhe-Sheng Chen,Amit K. Tiwari +8 more
TL;DR: In this article, the role of endolysosomal trafficking in multidrug resistance was discussed and targeted endosomal pathways could emerge as a new therapeutic strategy to overcome chemoresistance in cancer.
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