2020
DOI: 10.1016/j.celrep.2020.107775
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Synaptic Vesicle Precursors and Lysosomes Are Transported by Different Mechanisms in the Axon of Mammalian Neurons

Abstract: SUMMARY BORC is a multisubunit complex previously shown to promote coupling of mammalian lysosomes and C. elegans synaptic vesicle (SV) precursors (SVPs) to kinesins for anterograde transport of these organelles along microtubule tracks. We attempted to meld these observations into a unified model for axonal transport in mammalian neurons by testing two alternative hypotheses: (1) that SV and lysosomal proteins are co-transported within a single type of “lysosome-related vesic… Show more

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Cited by 52 publications
(47 citation statements)
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References 88 publications
(146 reference statements)
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“…We also detected larger light-lumen vesicles. These had a diameter of 70 - 170 nm and may correspond to less well characterized axonal compartments such as synaptic vesicle precursors or early endosomes (Pace et al, 2020; Wang et al, 2016; Wu et al, 2017). Vesicles with a dark lumen had an average diameter of 95 nm with the majority ranging from 70 to 120 nm.…”
Section: Resultsmentioning
confidence: 99%
“…We also detected larger light-lumen vesicles. These had a diameter of 70 - 170 nm and may correspond to less well characterized axonal compartments such as synaptic vesicle precursors or early endosomes (Pace et al, 2020; Wang et al, 2016; Wu et al, 2017). Vesicles with a dark lumen had an average diameter of 95 nm with the majority ranging from 70 to 120 nm.…”
Section: Resultsmentioning
confidence: 99%
“…At steady state, lysosomes exhibit a characteristic distribution, consisting of a densely packed population in the juxtanuclear area and a scattered population in the periphery of the cell (reviewed by (Ballabio and Bonifacino, 2020;Bonifacino and Neefjes, 2017). In polarized cells such as neurons, the peripheral population of lysosomes includes distinct pools in specialized domains of the cells (e.g., axon and dendrites) (De Pace et al, 2020;Farfel-Becker et al, 2019;Farias et al, 2017;Lee et al, 2011;Tsuruta and Dolmetsch, 2015). The overall distribution of lysosomes results from the integration of various processes, including tethering to other organelles such as the endoplasmic reticulum (ER) (Jongsma et al, 2016;Raiborg et al, 2015;Rocha et al, 2009;Saric et al, 2021) and mobilization by coupling to microtubule motors (Harada et al, 1998;Hollenbeck and Swanson, 1990).…”
Section: Discussionmentioning
confidence: 99%
“…For both GTPases, there must be other regulators that determine the interaction with alternative adaptors and, consequently, the direction of lysosome transport. Nevertheless, the role of ARL8 in anterograde transport seems to be dominant over that in retrograde transport, since depletion of ARL8 or its positive regulator BORC cause juxtanuclear clustering of lysosomes, whereas overexpression of ARL8 drives lysosomes to the cell periphery (De Pace et al, 2020;Farias et al, 2017;Guardia et al, 2016;Keren-Kaplan and Bonifacino, 2021;Korolchuk et al, 2011;Pu et al, 2015;Rosa-Ferreira and Munro, 2011). Future studies will have to address under what conditions ARL8 promotes lysosome retrograde transport mediated by RUFY3 and RUFY4.…”
Section: Discussionmentioning
confidence: 99%
“…It covers rather long distances and is affected by lysosome size [ 62 ]. As for other types of vesicle transport, it requires the interaction among motor proteins, regulators, and adaptors [ 63 ], although specific components such as BORC (BLOC-one-related complex, where BLOC stands for biogenesis of lysosome-related organelles complex) are required for the transport of lysosomes, but not of synaptic vesicle precursors in mammalian axons [ 64 ].…”
Section: Lysosomal Exocytosismentioning
confidence: 99%