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Licensed Unlicensed Requires Authentication Published by De Gruyter December 13, 2022

Molecular insights into endolysosomal microcompartment formation and maintenance

  • Daniel Kümmel EMAIL logo , Eric Herrmann , Lars Langemeyer and Christian Ungermann ORCID logo EMAIL logo
From the journal Biological Chemistry

Abstract

The endolysosomal system of eukaryotic cells has a key role in the homeostasis of the plasma membrane, in signaling and nutrient uptake, and is abused by viruses and pathogens for entry. Endocytosis of plasma membrane proteins results in vesicles, which fuse with the early endosome. If destined for lysosomal degradation, these proteins are packaged into intraluminal vesicles, converting an early endosome to a late endosome, which finally fuses with the lysosome. Each of these organelles has a unique membrane surface composition, which can form segmented membrane microcompartments by membrane contact sites or fission proteins. Furthermore, these organelles are in continuous exchange due to fission and fusion events. The underlying machinery, which maintains organelle identity along the pathway, is regulated by signaling processes. Here, we will focus on the Rab5 and Rab7 GTPases of early and late endosomes. As molecular switches, Rabs depend on activating guanine nucleotide exchange factors (GEFs). Over the last years, we characterized the Rab7 GEF, the Mon1-Ccz1 (MC1) complex, and key Rab7 effectors, the HOPS complex and retromer. Structural and functional analyses of these complexes lead to a molecular understanding of their function in the context of organelle biogenesis.


Corresponding authors: Daniel Kümmel, Institute of Biochemistry, University of Münster, Corrensstraße 36, D-48149 Münster, Germany, E-mail: ; and Christian Ungermann, Department of Biology/Chemistry, Biochemistry Section, Osnabrück University, Barbarastraße 13, D-49076 Osnabrück, Germany; and Center of Cellular Nanoanalytics (CellNanOs), Osnabrück University, Barbarastraße 11, D-49076 Osnabrück, Germany, E-mail:

Funding source: Deutsche Forschungsgemeinschaft

Award Identifier / Grant number: SFB 944 - P11

Award Identifier / Grant number: SFB 944 - P17

  1. Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This work was funded by DFG (SFB 944, project P11 to C.U., project P17 to D.K.).

  3. Conflict of interest statement: The authors declare no conflicts of interest regarding this article.

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Received: 2022-09-28
Accepted: 2022-11-22
Published Online: 2022-12-13
Published in Print: 2023-04-25

© 2022 Walter de Gruyter GmbH, Berlin/Boston

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