ArticlePLoS genetics2024
LRK-1/LRRK2 and AP-3 regulate trafficking of synaptic vesicle precursors through active zone protein SYD-2/Liprin-α.
Article in PLoS genetics, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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8 citing papers in PubMed.
- MYO5A-mediated stabilization promotes the acquisition of fusion competence in sealed autophagosomes.The EMBO journal · 2026Article
- IGF-like growth factors that couple food sensing to developmental decisions employ different release mechanisms in a single pair ofbioRxiv : the preprint server for biology · 2026Article
- Loss of SYD-2 leads to decreased short-term memory inmicroPublication biology · 2026Article
- Biogenesis and reformation of synaptic vesicles.The Journal of physiology · 2025Review
- Expansion of lysosomal capacity in early adult neurons driven by TFEB/HLH-30 protects dendrite maintenance during aging in Caenorhabditis elegans.PLoS biology · 2025Article
- Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects.Frontiers in cell and developmental biology · 2025Article
- Axonal mitochondria regulate gentle touch response through control of axonal actin dynamics.bioRxiv : the preprint server for biology · 2024Article
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Abstract
Synaptic vesicle proteins (SVps) are transported by the motor UNC-104/KIF1A. We show that SVps travel in heterogeneous carriers in C. elegans neuronal processes, with some SVp carriers co-transporting lysosomal proteins (SV-lysosomes). LRK-1/LRRK2 and the clathrin adaptor protein complex AP-3 play a critical role in the sorting of SVps and lysosomal proteins away from each other at the SV-lysosomal intermediate trafficking compartment. Both SVp carriers lacking lysosomal proteins and SV-lysosomes are dependent on the motor UNC-104/KIF1A for their transport. In lrk-1 mutants, both SVp carriers and SV-lysosomes can travel in axons in the absence of UNC-104, suggesting that LRK-1 plays an important role to enable UNC-104 dependent transport of synaptic vesicle proteins. Additionally, LRK-1 acts upstream of the AP-3 complex and regulates its membrane localization. In the absence of the AP-3 complex, the SV-lysosomes become more dependent on the UNC-104-SYD-2/Liprin-α complex for their transport. Therefore, SYD-2 acts to link upstream trafficking events with the transport of SVps likely through its interaction with the motor UNC-104. We further show that the mistrafficking of SVps into the dendrite in lrk-1 and apb-3 mutants depends on SYD-2, likely by regulating the recruitment of the AP-1/UNC-101. SYD-2 acts in concert with AP complexes to ensure polarized trafficking & transport of SVps.
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