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

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Abstract While synaptic vesicle proteins (SVPs) and lysosomal can be present together in axons, the origin of these compartments is unclear. These SV-lysosomes are however thought to segregate further SVPs proteins. In this study, we identify genes characterize a genetic pathway involved segregation neuronal cell body. We novel role for BORC (BLOC-1-related complex) segregating subunit SAM-4/Myrlysin acts through ARL-8 Kinesin motor UNC-116/KIF5 UNC-104/KIF1A Additionally, also show that LRK-1/LRRK2 APB-3/AP-3 (β3), pre-SV biogenesis, regulate LRK-1 recruits SAM-4 turn governs localisation APB-3 suggesting hierarchical LRK-1-SAM-4-APB-3 observe size protein-containing (LPCCs) smaller LRK-1. This regulation depends on UNC-116. Together, recruited by via motors along with AP-3 mediates

Language: Английский

---

Roles of LRRK2 and its orthologs in protecting against neurodegeneration and neurodevelopmental defects

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: April 30, 2025

In humans, variants in the LRRK2 gene are most prevalent risk factors for Parkinson's disease (PD). Whereas studies model organisms have long indicated that orthologs of wild-type LRRK proteins protect against neurodegeneration, newer findings indicate they also neurodevelopmental defects. This normal role can be disrupted by either gain-of-function (GOF) or loss-of-function (LOF) mutations, leading to neurodegeneration and Here, we review roles their these processes, with a focus on autophagy as common factor may mediate both roles. We highlight potential experiments vertebrate invertebrate systems synergistically inform our understanding protecting neurological disorders.

Language: Английский

---

Preferential transport of synaptic vesicles across neuronal branches is regulated by the levels of the anterograde motor UNC-104/KIF1A in vivo

Genetics, Journal Year: 2024, Volume and Issue: 227(1)

Published: Feb. 14, 2024

Abstract Asymmetric transport of cargo across axonal branches is a field active research. Mechanisms contributing to preferential along specific in vivo wild type neurons are poorly understood. We find that anterograde synaptic vesicles preferentially enter the branch or pause at point Caenorhabditis elegans Posterior Lateral Mechanosensory neurons. The vesicle kinesin motor UNC-104/KIF1A regulates this behavior point. Reduced levels functional UNC-104 cause predominantly and lose their preference for turning into branch. SAM-4/Myrlysin, which aids recruitment/activation on vesicles, similar UNC-104. Increasing increases go straight toward asynaptic end. This suggests neuron optimizes surface maximize fraction entering minimize going

Language: Английский

---

Biogenesis and reformation of synaptic vesicles

The Journal of Physiology, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 5, 2024

Abstract Communication within the nervous system relies on calcium‐triggered release of neurotransmitter molecules by exocytosis synaptic vesicles (SVs) at defined active zone sites. While decades research have provided detailed insight into molecular machinery for SV fusion, much less is known about mechanisms that form functional SVs during development synapses and control local reformation following in mature system. Here we review current state knowledge field, focusing pathways implicated formation axonal transport precursor organelles involved nerve terminals neurons. We discuss open questions outline perspectives future research. image

Language: Английский

---