Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Lund, Viktor K.; Lycas, Matthew D.; Schack, Anders; Andersen, Rita C.; Gether, Ulrik; Kjærulff, Ole

doi:10.1016/j.celrep.2021.108973

Cited by 29 publications

(32 citation statements)

References 80 publications

(125 reference statements)

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“…To label lysosomes, there are transgenic flies with genetically‐encoded fluorescent lysosome markers, like LAMP1 and Arl8, which are commonly used for in vivo analysis of lysosome morphology and motility. In addition to labelling lysosomes, it is also possible to co‐label other markers of interest ( e.g ., Rab7 and Atg8, to assess endocytic flux) 225‐228 . The expression of fluorescently labelled lysosomes can be performed in virtually any cell type or tissue of interest by using binary systems like the UAS/Gal4, LexAop/LexA or QUAS/QF 224,229,230 .…”

Section: Methods To Analyze Lysosome Morphology Positioning Motility ...mentioning

confidence: 99%

“…In addition to labelling lysosomes, it is also possible to co-label other markers of interest (e.g., Rab7 and Atg8, to assess endocytic flux). [225][226][227][228] The expression of fluorescently labelled lysosomes can be performed in virtually any cell type or tissue of interest by using binary systems like the UAS/Gal4, LexAop/LexA or QUAS/QF. 224,229,230 Lysosome motility can also be analyzed and quantified by expressing fluorescently labelled lysosome markers in specific tissues and using standard methods described above (e.g., kymographs, see Section 4.9.2).…”

Section: Analysing Lysosome Motility In Vivomentioning

confidence: 99%

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Current methods to analyze lysosome morphology, positioning, motility and function

Barral

Staiano

Almeida

et al. 2022

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Since the discovery of lysosomes more than 70 years ago, much has been learned about the functions of these organelles. Lysosomes were regarded as exclusively degradative organelles, but more recent research has shown that they play essential roles in several other cellular functions, such as nutrient sensing, intracellular signalling and metabolism. Methodological advances played a key part in generating our current knowledge about the biology of this multifaceted organelle. In this review, we cover current methods used to analyze lysosome morphology, positioning, motility and function. We highlight the principles behind these methods, the methodological strategies and their advantages and limitations. To extract accurate information and avoid misinterpretations, we discuss the best strategies to identify lysosomes and assess their characteristics and functions. With this review, we aim to stimulate an increase in the quantity and quality of research on lysosomes and further ground‐breaking discoveries on an organelle that continues to surprise and excite cell biologists.

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Section: Methods To Analyze Lysosome Morphology Positioning Motility ...mentioning

confidence: 99%

Section: Analysing Lysosome Motility In Vivomentioning

confidence: 99%

Current methods to analyze lysosome morphology, positioning, motility and function

Barral

Staiano

Almeida

et al. 2022

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“…Interestingly, Arl8 interaction with KIF1A or its ortholog UNC-104 also mediates the plus end–directed transport of dense core vesicles (DCVs; Hummel and Hoogenraad, 2021 ; Lund et al, 2021 ) and synaptic vesicle precursors (SVPs; Niwa et al, 2017 ; Vukoja et al, 2018 ; Wu et al, 2013 ). Overlap between the axonal transport machinery of DCVs and lysosomes was also observed in Drosophila brains, where Arl8 promoted DCV movement into axons while Rab2 was required for the bidirectional transport of both DCVs and lysosomal organelles along axonal processes ( Lund et al, 2021 ). Interestingly, LEs/lysosomes can also act as “hitchhiking” platforms for RNA granule transport ( Cioni et al, 2019 ; Corradi et al, 2020 ; Liao et al, 2019 ).…”

Section: Endolysosome Transport Machinerymentioning

confidence: 99%

Neuronal endolysosomal transport and lysosomal functionality in maintaining axonostasis

Roney

Cheng

Sheng

2022

Journal of Cell Biology

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Lysosomes serve as degradation hubs for the turnover of endocytic and autophagic cargos, which is essential for neuron function and survival. Deficits in lysosome function result in progressive neurodegeneration in most lysosomal storage disorders and contribute to the pathogenesis of aging-related neurodegenerative diseases. Given their size and highly polarized morphology, neurons face exceptional challenges in maintaining cellular homeostasis in regions far removed from the cell body where mature lysosomes are enriched. Neurons therefore require coordinated bidirectional intracellular transport to sustain efficient clearance capacity in distal axonal regions. Emerging lines of evidence have started to uncover mechanisms and signaling pathways regulating endolysosome transport and maturation to maintain axonal homeostasis, or “axonostasis,” that is relevant to a range of neurologic disorders. In this review, we discuss recent advances in how axonal endolysosomal trafficking, distribution, and lysosomal functionality support neuronal health and become disrupted in several neurodegenerative diseases.

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“…Our results show that Wnt3 is also distributed in a vesicular-like pattern in NSC-34 cells that resembles the distribution of the SV2 marker, a membrane glycoprotein localized in neuronal secretory vesicles [ 35 ]. Our findings show that the vesicular-like distribution of Wnt3HA does not colocalize with the exosome marker, nor with BDNF dense core vesicles (DCV) or with Rab11, which opens the possibility that the transport of Wnt3 secretory vesicles along motor axons could be driven by other monomeric GTPases that are known to mediate the axonal transport of different vesicles, such as Rab2, Rab27a, or Rab3 [ 36 , 37 , 38 ]. In addition, future studies should consider other general markers of secretory vesicles, including SNARE proteins such as synaptobrevin 2 and synaptotagmins, as these proteins likely control the secretion of different subsets of secretory vesicles in axons [ 24 , 39 , 40 ].…”

Section: Discussionmentioning

confidence: 99%

Transport and Secretion of the Wnt3 Ligand by Motor Neuron-like Cells and Developing Motor Neurons

et al. 2021

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The vertebrate neuromuscular junction (NMJ) is formed by a presynaptic motor nerve terminal and a postsynaptic muscle specialization. Cumulative evidence reveals that Wnt ligands secreted by the nerve terminal control crucial steps of NMJ synaptogenesis. For instance, the Wnt3 ligand is expressed by motor neurons at the time of NMJ formation and induces postsynaptic differentiation in recently formed muscle fibers. However, the behavior of presynaptic-derived Wnt ligands at the vertebrate NMJ has not been deeply analyzed. Here, we conducted overexpression experiments to study the expression, distribution, secretion, and function of Wnt3 by transfection of the motor neuron-like NSC-34 cell line and by in ovo electroporation of chick motor neurons. Our findings reveal that Wnt3 is transported along motor axons in vivo following a vesicular-like pattern and reaches the NMJ area. In vitro, we found that endogenous Wnt3 expression increases as the differentiation of NSC-34 cells proceeds. Although NSC-34 cells overexpressing Wnt3 do not modify their morphological differentiation towards a neuronal phenotype, they effectively induce acetylcholine receptor clustering on co-cultured myotubes. These findings support the notion that presynaptic Wnt3 is transported and secreted by motor neurons to induce postsynaptic differentiation in nascent NMJs.

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Rab2 drives axonal transport of dense core vesicles and lysosomal organelles

Cited by 29 publications

References 80 publications

Current methods to analyze lysosome morphology, positioning, motility and function

Current methods to analyze lysosome morphology, positioning, motility and function

Neuronal endolysosomal transport and lysosomal functionality in maintaining axonostasis

Transport and Secretion of the Wnt3 Ligand by Motor Neuron-like Cells and Developing Motor Neurons

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