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bioRxiv · 10.1101/2024.12.31.630845

BORC segregates synaptic vesicle and lysosomal proteins through motors UNC-104/KIF1A and UNC-116/KIF5

Mathew, A.·Seal, S.·Dandekar, A.·Chauhan, B. S.·Sivadasan, S.·Nonet, M. L.·Koushika, S. P.
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Abstract

While synaptic vesicle proteins (SVPs) and lysosomal proteins can be present together in axons, the origin of these compartments is unclear. These SV-lysosomes are however thought to segregate further to SVPs and lysosomal proteins. In this study, we identify genes and characterize a genetic pathway involved in the segregation of SVPs and lysosomal proteins in the neuronal cell body. We identify a novel role for BORC (BLOC-1-related complex) in segregating SVPs and lysosomal proteins in the cell body. BORC subunit SAM-4/Myrlysin acts through ARL-8 and Kinesin motor proteins UNC-116/KIF5 and UNC-104/KIF1A in segregating SVPs and lysosomal proteins. Additionally, we also show that LRK-1/LRRK2 and APB-3/AP-3 ({beta}3), involved in pre-SV biogenesis, regulate the segregation of SVPs and lysosomal proteins in the neuronal cell body. LRK-1 recruits SAM-4 that in turn governs the localisation of APB-3 suggesting a hierarchical pathway of LRK-1-SAM-4-APB-3 for the segregation of SVPs and lysosomal proteins. Additionally, we also observe that the size of lysosomal protein-containing compartments (LPCCs) is smaller in SAM-4 and LRK-1. This size regulation depends on UNC-116. Together, we show that BORC recruited by LRK-1 and in turn via motors and along with AP-3 mediates the segregation of SVPs and lysosomal proteins in the neuronal cell body.

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Mathew, A., Seal, S., Dandekar, A., Chauhan, B. S., Sivadasan, S., Nonet, M. L., Koushika, S. P.. 2025-01-01. BORC segregates synaptic vesicle and lysosomal proteins through motors UNC-104/KIF1A and UNC-116/KIF5. https://doi.org/10.1101/2024.12.31.630845

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