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Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo

Lysosomes are well-established as the main cellular organelles for the degradation of macromolecules and emerging as regulatory centers of metabolism. They are of crucial importance for cellular homeostasis, which is exemplified by a plethora of disorders related to alterations in lysosomal function...

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Autores principales: Singh, Jasjot, Elhabashy, Hadeer, Muthukottiappan, Pathma, Stepath, Markus, Eisenacher, Martin, Kohlbacher, Oliver, Gieselmann, Volkmar, Winter, Dominic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584938/
https://www.ncbi.nlm.nih.gov/pubmed/36266287
http://dx.doi.org/10.1038/s41467-022-33951-0
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author Singh, Jasjot
Elhabashy, Hadeer
Muthukottiappan, Pathma
Stepath, Markus
Eisenacher, Martin
Kohlbacher, Oliver
Gieselmann, Volkmar
Winter, Dominic
author_facet Singh, Jasjot
Elhabashy, Hadeer
Muthukottiappan, Pathma
Stepath, Markus
Eisenacher, Martin
Kohlbacher, Oliver
Gieselmann, Volkmar
Winter, Dominic
author_sort Singh, Jasjot
collection PubMed
description Lysosomes are well-established as the main cellular organelles for the degradation of macromolecules and emerging as regulatory centers of metabolism. They are of crucial importance for cellular homeostasis, which is exemplified by a plethora of disorders related to alterations in lysosomal function. In this context, protein complexes play a decisive role, regulating not only metabolic lysosomal processes but also lysosome biogenesis, transport, and interaction with other organelles. Using cross-linking mass spectrometry, we analyze lysosomes and early endosomes. Based on the identification of 5376 cross-links, we investigate protein-protein interactions and structures of lysosome- and endosome-related proteins. In particular, we present evidence for a tetrameric assembly of the lysosomal hydrolase PPT1 and a heterodimeric structure of FLOT1/FLOT2 at lysosomes and early endosomes. For FLOT1-/FLOT2-positive early endosomes, we identify >300 putative cargo proteins and confirm eleven substrates for flotillin-dependent endocytosis, including the latrophilin family of adhesion G protein-coupled receptors.
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spelling pubmed-95849382022-10-22 Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo Singh, Jasjot Elhabashy, Hadeer Muthukottiappan, Pathma Stepath, Markus Eisenacher, Martin Kohlbacher, Oliver Gieselmann, Volkmar Winter, Dominic Nat Commun Article Lysosomes are well-established as the main cellular organelles for the degradation of macromolecules and emerging as regulatory centers of metabolism. They are of crucial importance for cellular homeostasis, which is exemplified by a plethora of disorders related to alterations in lysosomal function. In this context, protein complexes play a decisive role, regulating not only metabolic lysosomal processes but also lysosome biogenesis, transport, and interaction with other organelles. Using cross-linking mass spectrometry, we analyze lysosomes and early endosomes. Based on the identification of 5376 cross-links, we investigate protein-protein interactions and structures of lysosome- and endosome-related proteins. In particular, we present evidence for a tetrameric assembly of the lysosomal hydrolase PPT1 and a heterodimeric structure of FLOT1/FLOT2 at lysosomes and early endosomes. For FLOT1-/FLOT2-positive early endosomes, we identify >300 putative cargo proteins and confirm eleven substrates for flotillin-dependent endocytosis, including the latrophilin family of adhesion G protein-coupled receptors. Nature Publishing Group UK 2022-10-20 /pmc/articles/PMC9584938/ /pubmed/36266287 http://dx.doi.org/10.1038/s41467-022-33951-0 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Singh, Jasjot
Elhabashy, Hadeer
Muthukottiappan, Pathma
Stepath, Markus
Eisenacher, Martin
Kohlbacher, Oliver
Gieselmann, Volkmar
Winter, Dominic
Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
title Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
title_full Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
title_fullStr Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
title_full_unstemmed Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
title_short Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
title_sort cross-linking of the endolysosomal system reveals potential flotillin structures and cargo
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9584938/
https://www.ncbi.nlm.nih.gov/pubmed/36266287
http://dx.doi.org/10.1038/s41467-022-33951-0
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