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

Author

Listed:
  • Jasjot Singh

    (University of Bonn)

  • Hadeer Elhabashy

    (Max-Planck-Institute for Developmental Biology
    University of Tübingen
    University of Tübingen)

  • Pathma Muthukottiappan

    (University of Bonn)

  • Markus Stepath

    (Ruhr-University Bochum
    Ruhr-University Bochum)

  • Martin Eisenacher

    (Ruhr-University Bochum
    Ruhr-University Bochum)

  • Oliver Kohlbacher

    (University of Tübingen
    University of Tübingen
    University Hospital Tübingen)

  • Volkmar Gieselmann

    (University of Bonn)

  • Dominic Winter

    (University of Bonn)

Abstract

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.

Suggested Citation

  • Jasjot Singh & Hadeer Elhabashy & Pathma Muthukottiappan & Markus Stepath & Martin Eisenacher & Oliver Kohlbacher & Volkmar Gieselmann & Dominic Winter, 2022. "Cross-linking of the endolysosomal system reveals potential flotillin structures and cargo," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-33951-0
    DOI: 10.1038/s41467-022-33951-0
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