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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, Morrison, Logan M, Yorks, Rosalina M, Hoover, Christopher M, Boominathan, Soorajnath, Miller, Kenneth G·2015·Genetics
DOI 10.1534/genetics.115.177345
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Abstract

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.

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  • The phenotype of Y71H2AM.2(null) worms reflects in many regards that of worms depleted of the JIP3/4 homolog UNC-16, in particular the redistribution of lysosomes to the more proximal axon.

    “The phenotype of the Y71H2AM.2(null)worms interestingly reflects in many regards that of worms depleted of the JIP3/4 homolog UNC-16 (the C. elegans homolog of JIP3/4), in particular the redistribution of lysosomes to the more proximal axon (Celestino et al., 2022;Edwards et al., 2015;Edwards et al., 2013)”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Edwards et al., 2015

  • UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null) worms.

    “However, UNC-16-deficient worms show a clearly aggravated phenotype, including uncoordinated movement, which is not the case for Y71H2AM.2(null)worms”

    From TMEM55B promotes anterograde transport and distal axonal distribution of LAMP1-positive organelles (2026) · cites this paper as Edwards et al., 2015

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Metadata

Authors
Edwards, S. L., Morrison, L. M., Yorks, R. M., Hoover, C. M., Boominathan, S., & Miller, K. G.
Affiliations
Genetic Models of Disease Laboratory, Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma 73104
Venue
Genetics
Publisher
Oxford University Press (OUP)
Published
2015-09-01
Volume
201
Issue
1
Pages
117-141
ISSN
1943-2631
DOI
10.1534/genetics.115.177345
Cited by
34
References
7
Language
en
Licence
academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model (vor)

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