Synaptic Vesicle Precursors and Lysosomes Are Transported by Different Mechanisms in the Axon of Mammalian Neurons

• Published in: Cell reports (Cambridge) 2020-06, Vol.31 (11), p.107775-107775, Article 107775
• Main Authors: De Pace, Raffaella, Britt, Dylan J., Mercurio, Jeffrey, Foster, Arianne M., Djavaherian, Lucas, Hoffmann, Victoria, Abebe, Daniel, Bonifacino, Juan S.
• Format: Article
• Language: English
• Subjects: ARL8; axonal transport; BORC; corpus callosum; hippocampus; kinesins; lysosomes; microtubules; neuromuscular junction; synaptic vesicle precursors
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2020.107775

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 vesicle” and (2) that SVPs and lysosomes are distinct organelles, but both depend on BORC for axonal transport. Analyses of various types of neurons from wild-type rats and mice, as well as from BORC-deficient mice, show that neither hypothesis is correct. We find that SVPs and lysosomes are transported separately, but only lysosomes depend on BORC for axonal transport in these neurons. These findings demonstrate that SVPs and lysosomes are distinct organelles that rely on different machineries for axonal transport in mammalian neurons. [Display omitted] •Lysosomes and synaptic vesicle precursors (SVPs) move separately in mammalian axons•BORC is required for transport of lysosomes but not SVPs in mammalian axons•BORC-subunit knockout causes axon swellings and neonatal death in mice•Defective axonal lysosome transport may underlie pathology of human BORC deficiency De Pace et al. show that lysosomes and synaptic vesicle precursors (SVPs) are distinct organelles that move separately from the soma to the axon in rat and mouse neurons. Moreover, they demonstrate that the BLOC-1-related complex (BORC) is required for the transport of lysosomes but not SVPs in mouse neurons.