UNC-16 (JIP3) Acts Through Synapse-Assembly Proteins to Inhibit the Active Transport of Cell Soma Organelles to Caenorhabditis elegans Motor Neuron Axons

摘要

The conserved protein [UNC-16][1] (JIP3) inhibits the active transport of some cell soma organelles, such as lysosomes, early endosomes, and Golgi, to the synaptic region of axons. However, little is known about [UNC-16][1]’s organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an [unc-16][1] suppressor screen in Caenorhabditis elegans to discover that [UNC-16][1] acts through [CDK-5][2] (Cdk5) and two conserved synapse assembly proteins: [SAD-1][3] (SAD-A Kinase), and [SYD-2][4] (Liprin-α). Genetic analysis of all combinations of double and triple mutants in [unc-16][1](+) and [unc-16][1](?) backgrounds showed that the three proteins (CDK-5, SAD-1, and SYD-2) are all part of the same organelle transport regulatory system, which we named the CSS system based on its founder proteins. Further genetic analysis revealed roles for [SYD-1][5] (another synapse assembly protein) and STRADα (a [SAD-1][3]-interacting protein) in the CSS system. In an [unc-16][1](?) background, loss of the CSS system improved the sluggish locomotion of [unc-16][1] mutants, inhibited axonal lysosome accumulation, and led to the dynein-dependent accumulation of lysosomes in dendrites. Time-lapse imaging of lysosomes in CSS system mutants in [unc-16][1](+) and [unc-16][1](?) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. [UNC-16][1] also uses the CSS system to regulate the distribution of early endosomes in neurons and, to a lesser extent, Golgi. The data reveal a new and unprecedented role for synapse assembly proteins, acting as part of the newly defined CSS system, in mediating [UNC-16][1]’s organelle transport regulatory function. [1]: http://www.wormbase.org/db/get?name=WBGene00006755;class=Gene [2]: http://www.wormbase.org/db/get?name=WBGene00000407;class=Gene [3]: http://www.wormbase.org/db/get?name=WBGene00004719;class=Gene [4]: http://www.wormbase.org/db/get?name=WBGene00006364;class=Gene [5]: http://www.wormbase.org/db/get?name=WBGene00006363;class=Gene