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The Endosomal-Lysosomal System: A Dynamic Network of Molecular and Cellular Pathways

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 11946

Special Issue Editors

Department of Life Science, University of Siena, 4 53100 Siena, Italy
Interests: vesicular trafficking; immune synapse; T- and B- lymphocytes

E-Mail Website1 Website2
Guest Editor
Department of Life Sciences, University of Siena, Siena, Italy
Interests: vesicular trafficking; intraflagellar transport; autophagy; lysosomes; immunological synapse; T and B lymphocytes

Special Issue Information

Dear Colleagues,

The endosomal-lysosomal system is a highly dynamic network of intracellular membranous compartments where different trafficking pathways converge to regulate the delivery and localization of cargo molecules as well as their processing. The active transport through these compartments is based on endocytosis and exocytosis and exploits the tight coordination of several molecular mechanisms to control both endosome processing and cargo sorting. The endosomal-lysosomal system is essential for cell physiology and is involved in maintaining cellular homeostasis and supporting organism development and growth. Accordingly, defective endosomal trafficking is considered to be a pathogenic factor in a number of diseases, including metabolic and neurodegenerative disorders, immune diseases and cancer. 

This Special Issue aims to cover research dissecting the molecular and cellular mechanisms involved in the formation and maturation of endosomes/lysosomes, vesicle trafficking, protein sorting and targeted degradation of specific cargoes. We will explore the role of endosomal/lysosomal system in health and disease and address how this system may be targeted for therapeutic purposes.

Dr. Anna Onnis
Dr. Francesca Finetti
Guest Editors

Manuscript Submission Information

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Keywords

  • endosomes
  • lysosomes
  • vesicular trafficking
  • endocytosis
  • exocytosis
  • protein sorting
  • cargo degradation

Published Papers (4 papers)

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Research

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12 pages, 4192 KiB  
Article
Drosophila Rab39 Attenuates Lysosomal Degradation
by Zsolt Lakatos, Péter Benkő, Gábor Juhász and Péter Lőrincz
Int. J. Mol. Sci. 2021, 22(19), 10635; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms221910635 - 30 Sep 2021
Cited by 2 | Viewed by 2178
Abstract
Lysosomal degradation, the common destination of autophagy and endocytosis, is one of the most important elements of eukaryotic metabolism. The small GTPases Rab39A and B are potential new effectors of this pathway, as their malfunction is implicated in severe human diseases like cancer [...] Read more.
Lysosomal degradation, the common destination of autophagy and endocytosis, is one of the most important elements of eukaryotic metabolism. The small GTPases Rab39A and B are potential new effectors of this pathway, as their malfunction is implicated in severe human diseases like cancer and neurodegeneration. In this study, the lysosomal regulatory role of the single Drosophila Rab39 ortholog was characterized, providing valuable insight into the potential cell biological mechanisms mediated by these proteins. Using a de novo CRISPR-generated rab39 mutant, we found no failure in the early steps of endocytosis and autophagy. On the contrary, we found that Rab39 mutant nephrocytes internalize and degrade endocytic cargo at a higher rate compared to control cells. In addition, Rab39 mutant fat body cells contain small yet functional autolysosomes without lysosomal fusion defect. Our data identify Drosophila Rab39 as a negative regulator of lysosomal clearance during both endocytosis and autophagy. Full article
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Review

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13 pages, 1290 KiB  
Review
IFT20: An Eclectic Regulator of Cellular Processes beyond Intraflagellar Transport
by Francesca Finetti, Anna Onnis and Cosima T. Baldari
Int. J. Mol. Sci. 2022, 23(20), 12147; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232012147 - 12 Oct 2022
Cited by 2 | Viewed by 2146
Abstract
Initially discovered as the smallest component of the intraflagellar transport (IFT) system, the IFT20 protein has been found to be implicated in several unconventional mechanisms beyond its essential role in the assembly and maintenance of the primary cilium. IFT20 is now considered a [...] Read more.
Initially discovered as the smallest component of the intraflagellar transport (IFT) system, the IFT20 protein has been found to be implicated in several unconventional mechanisms beyond its essential role in the assembly and maintenance of the primary cilium. IFT20 is now considered a key player not only in ciliogenesis but also in vesicular trafficking of membrane receptors and signaling proteins. Moreover, its ability to associate with a wide array of interacting partners in a cell-type specific manner has expanded the function of IFT20 to the regulation of intracellular degradative and secretory pathways. In this review, we will present an overview of the multifaceted role of IFT20 in both ciliated and non-ciliated cells. Full article
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27 pages, 3742 KiB  
Review
Endocytosis at the Crossroad of Polarity and Signaling Regulation: Learning from Drosophila melanogaster and Beyond
by Fani Papagiannouli
Int. J. Mol. Sci. 2022, 23(9), 4684; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23094684 - 23 Apr 2022
Cited by 2 | Viewed by 4225
Abstract
Cellular trafficking through the endosomal–lysosomal system is essential for the transport of cargo proteins, receptors and lipids from the plasma membrane inside the cells and across membranous organelles. By acting as sorting stations, vesicle compartments direct the fate of their content for degradation, [...] Read more.
Cellular trafficking through the endosomal–lysosomal system is essential for the transport of cargo proteins, receptors and lipids from the plasma membrane inside the cells and across membranous organelles. By acting as sorting stations, vesicle compartments direct the fate of their content for degradation, recycling to the membrane or transport to the trans-Golgi network. To effectively communicate with their neighbors, cells need to regulate their compartmentation and guide their signaling machineries to cortical membranes underlying these contact sites. Endosomal trafficking is indispensable for the polarized distribution of fate determinants, adaptors and junctional proteins. Conversely, endocytic machineries cooperate with polarity and scaffolding components to internalize receptors and target them to discrete membrane domains. Depending on the cell and tissue context, receptor endocytosis can terminate signaling responses but can also activate them within endosomes that act as signaling platforms. Therefore, cell homeostasis and responses to environmental cues rely on the dynamic cooperation of endosomal–lysosomal machineries with polarity and signaling cues. This review aims to address advances and emerging concepts on the cooperative regulation of endocytosis, polarity and signaling, primarily in Drosophila melanogaster and discuss some of the open questions across the different cell and tissue types that have not yet been fully explored. Full article
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16 pages, 1585 KiB  
Review
Deliver on Time or Pay the Fine: Scheduling in Membrane Trafficking
by Giampaolo Placidi and Carlo C. Campa
Int. J. Mol. Sci. 2021, 22(21), 11773; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms222111773 - 29 Oct 2021
Cited by 5 | Viewed by 2399
Abstract
Membrane trafficking is all about time. Automation in such a biological process is crucial to ensure management and delivery of cellular cargoes with spatiotemporal precision. Shared molecular regulators and differential engagement of trafficking components improve robustness of molecular sorting. Sequential recruitment of low [...] Read more.
Membrane trafficking is all about time. Automation in such a biological process is crucial to ensure management and delivery of cellular cargoes with spatiotemporal precision. Shared molecular regulators and differential engagement of trafficking components improve robustness of molecular sorting. Sequential recruitment of low affinity protein complexes ensures directionality of the process and, concomitantly, serves as a kinetic proofreading mechanism to discriminate cargoes from the whole endocytosed material. This strategy helps cells to minimize losses and operating errors in membrane trafficking, thereby matching the appealed deadline. Here, we summarize the molecular pathways of molecular sorting, focusing on their timing and efficacy. We also highlight experimental procedures and genetic approaches to robustly probe these pathways, in order to guide mechanistic studies at the interface between biochemistry and quantitative biology. Full article
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