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.
Subject(s)
Adaptor Protein Complex 3 , Caenorhabditis elegans Proteins , Caenorhabditis elegans , Lysosomes , Nerve Tissue Proteins , Synaptic Vesicles , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Synaptic Vesicles/metabolism , Synaptic Vesicles/genetics , Adaptor Protein Complex 3/metabolism , Adaptor Protein Complex 3/genetics , Lysosomes/metabolism , Lysosomes/genetics , Nerve Tissue Proteins/metabolism , Nerve Tissue Proteins/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics , Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/metabolism , Protein Transport , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Neurons/metabolism , Kinesins/metabolism , Kinesins/genetics , Intracellular Signaling Peptides and Proteins/metabolism , Intracellular Signaling Peptides and Proteins/genetics , Axons/metabolism , Intercellular Signaling Peptides and ProteinsABSTRACT
In the following pages, we share a collection of photos, drawings, and mixed-media creations, most of them especially made for this JoN issue, manifesting C. elegans researchers' affection for their model organism and the founders of the field. This is a celebration of our community's growth, flourish, spread, and bright future. Descriptions provided by the contributors, edited for space. 1.
