<i>Drosophila</i>
            Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

Lund, Viktor K.; Madsen, Kenneth L.; Kjærulff, Ole

doi:10.1080/15548627.2018.1458170

Cited by 37 publications

(52 citation statements)

References 96 publications

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“…Likewise, Arl8 is a central regulator of lysosomal transport (Farias et al, 2017;Rosa-Ferreira and Munro, 2011;Vukoja et al, 2018). This illustrates an intriguing parallel between the biology of DCVs and lysosomes, reinforced by the fact that Rab2 is involved the biogenesis of both lysosomes (Lorincz et al, 2017;Lund et al, 2018) and…”

Section: Discussionmentioning

confidence: 91%

“…Therefore, the apparent alterations in DCV axonal transport are not caused by rerouting of DCV cargo to LEs, which are expected to have different transport characteristics than bona fide DCVs. Importantly, Vps39 Δ1 hemizygous null mutant larvae, in which LE-lysosome fusion is blocked as in Rab2 nulls (Lorincz et al, 2017;Lund et al, 2018), did not display the defects in transport of Ilp2-GFP-positive DCVs in motor axons that characterized Rab2 Δ1 animals ( Fig. 3B-E).…”

Section: Rab2 Is Required For DCV Axonal Transportmentioning

confidence: 91%

“…Rab2 is closely associated with the function of the endolysosomal system and is present on the membranes of endosomes and lysosomes, albeit transiently or in very low abundance in most cell types (Gillingham et al, 2014;Lorincz et al, 2017;Lund et al, 2018). Accordingly, both EEs, marked by GFP-Rab5 and LEs, marked by GFP-Rab7, showed markedly reduced motility in peripheral motor axons in the absence of Rab2.…”

Section: Rab2 Controls Axonal Transport Of Endosomes and Lysosomal Ormentioning

confidence: 99%

“…However, with standard confocal live imaging GFP-Rab2 appeared to be largely diffusely distributed in peripheral nerves, with occasional strongly labeled immobile organelles. We reasoned that if Rab2 is present on the membranes of moving DCVs it might be in very low abundance or very transiently, similar to its fleeting interaction with endosomal membranes (Lorincz et al, 2017;Lund et al, 2018). Moreover, its presence on the DCVs would be obscured by cytosolic Rab2 in the axoplasm and in the surrounding glial sheath.…”

Section: Rab2 Is Present On Moving Dcvsmentioning

confidence: 99%

“…Recently, we and others reported that Rab2 is critical for biogenesis of mature degradative endoand autolysosomal compartments by controlling the fusion of late endosomes (LEs) with lysosomes and transport vesicles carrying lysosomal membrane proteins, and fusion of autophagosomes with endolysosomal organelles (Lorincz et al, 2017;Lund et al, 2018) (Ding et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

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Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Lund

Lycas

Schack

et al. 2020

Preprint

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Long range fast axonal transport of neuropeptide-containing dense core vesicles (DCVs), endolysosomal organelles and presynaptic components is critical for maintaining the functionality of neurons. How the transport of DCVs is orchestrated remains an important unresolved question.The small GTPase Rab2 has previously been shown to mediate DCV biogenesis and endosomelysosome fusion. Here we use the Drosophila model system to demonstrate that Rab2 also plays a critical role in bidirectional axonal transport of DCVs, endosomes and lysosomal organelles, most likely by controlling molecular motors. We further show that the lysosomal motility factor Arl8 is required as well for axonal transport of DCVs, but unlike Rab2 is also critical for DCV exit from cell bodies into axons. Our results uncover the mechanisms responsible for axonal transport of DCVs and reveal surprising parallels between the regulation of DCVs and lysosomal motility.

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Section: Discussionmentioning

confidence: 91%

Section: Rab2 Is Required For DCV Axonal Transportmentioning

confidence: 91%

Section: Rab2 Controls Axonal Transport Of Endosomes and Lysosomal Ormentioning

confidence: 99%

Section: Rab2 Is Present On Moving Dcvsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Lund

Lycas

Schack

et al. 2020

Preprint

Self Cite

View full text Add to dashboard Cite

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Crosstalk between Endo/Exocytosis and Autophagy in Health and Disease

Papandreou

Tavernarakis

2020

Biotechnology Journal

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Imbalance between the main intracellular degradative, trafficking and intercellular shuttling pathways has been implicated in disease pathogenesis. Autophagy controls degradation of cellular components, while vesicular trafficking permits transport of material in and out of the cell. Emerging evidence has uncovered the extensive interconnectivity between these pathways, which is crucial to maintain organismal homeostasis. Thus, therapeutic intervention and drug development strategies targeting these processes, particularly in neurodegeneration, should account for this broad crosstalk, to maximize effectiveness. Here, recent findings underlining the highly dynamic nature of the crosstalk between autophagy, endosomal transport, and secretion is reviewed. Synergy of autophagy and endosomes for degradation, as well as, competition of autophagy and secretion are discussed. Perturbation of this crosstalk triggers pathology especially neurodegeneration.

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Apical-basal polarity regulators are essential for slit diaphragm assembly and endocytosis in Drosophila nephrocytes

Heiden

Siwek

Lotz

et al. 2021

Cell. Mol. Life Sci.

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Apical-basal polarity is a key feature of most epithelial cells and it is regulated by highly conserved protein complexes. In mammalian podocytes, which emerge from columnar epithelial cells, this polarity is preserved and the tight junctions are converted to the slit diaphragms, establishing the filtration barrier. In Drosophila, nephrocytes show several structural and functional similarities with mammalian podocytes and proximal tubular cells. However, in contrast to podocytes, little is known about the role of apical-basal polarity regulators in these cells. In this study, we used expansion microscopy and found the apical polarity determinants of the PAR/aPKC and Crb-complexes to be predominantly targeted to the cell cortex in proximity to the nephrocyte diaphragm, whereas basolateral regulators also accumulate intracellularly. Knockdown of PAR-complex proteins results in severe endocytosis and nephrocyte diaphragm defects, which is due to impaired aPKC recruitment to the plasma membrane. Similar, downregulation of most basolateral polarity regulators disrupts Nephrin localization but had surprisingly divergent effects on endocytosis. Our findings suggest that morphology and slit diaphragm assembly/maintenance of nephrocytes is regulated by classical apical-basal polarity regulators, which have distinct functions in endocytosis.

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Drosophila Rab2 controls endosome-lysosome fusion and LAMP delivery to late endosomes

Cited by 37 publications

References 96 publications

Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Crosstalk between Endo/Exocytosis and Autophagy in Health and Disease

Apical-basal polarity regulators are essential for slit diaphragm assembly and endocytosis in Drosophila nephrocytes

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