Journal Article

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

Edwards, Stacey L, Hoover, Christopher M, Miller, Kenneth G, Yorks, Rosalina M, Boominathan, Soorajnath, Morrison, Logan M

2015

Overview

The conserved protein UNC-16 (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’s organelle transport regulatory function, which is distinct from its Kinesin-1 adaptor function. We used an unc-16 suppressor screen in Caenorhabditis elegans to discover that UNC-16 acts through CDK-5 (Cdk5) and two conserved synapse assembly proteins: SAD-1 (SAD-A Kinase), and SYD-2 (Liprin-α). Genetic analysis of all combinations of double and triple mutants in unc-16(+) and unc-16(−) 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 (another synapse assembly protein) and STRADα (a SAD-1-interacting protein) in the CSS system. In an unc-16(−) background, loss of the CSS system improved the sluggish locomotion of unc-16 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(+) and unc-16(−) backgrounds revealed active transport defects consistent with the steady-state distributions of lysosomes. UNC-16 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’s organelle transport regulatory function.

• Publisher: Genetics Society of America
• Subject: Adaptor Proteins, Signal Transducing - genetics / Adaptor Proteins, Signal Transducing - metabolism / Animals / Axons - metabolism / Biological Transport, Active / Caenorhabditis elegans / Caenorhabditis elegans - metabolism / Caenorhabditis elegans Proteins - genetics / Caenorhabditis elegans Proteins - metabolism / Cells / Cyclin-Dependent Kinase 5 - metabolism / Intercellular Signaling Peptides and Proteins / Intracellular Signaling Peptides and Proteins - metabolism / Investigations / Motor Neurons - metabolism / Neurons / Organelles - metabolism / Organisms / Phosphoproteins - metabolism / Protein Serine-Threonine Kinases - metabolism / Proteins