Journal
NEUROSCIENTIST
Volume 23, Issue 3, Pages 232-250Publisher
SAGE PUBLICATIONS INC
DOI: 10.1177/1073858416648307
Keywords
Caenorhabditis elegans; Zebrafish; axonal transport; active zone; dynein; JIP3 (JSAP1); SYD-2 (Liprin-alpha); Cdk5; SAD kinase; BRSK1
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Funding
- National Institute of General Medical Sciences of the National Institutes of Health [R01GM080765]
- Oklahoma Center for the Advancement of Science and Technology [HR14-003]
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In neurons, a single motor (dynein) transports large organelles as well as synaptic and dense core vesicles toward microtubule minus ends; however, it is unclear why dynein appears more active on organelles, which are generally excluded from mature axons, than on synaptic and dense core vesicles, which are maintained at high levels. Recent studies in Zebrafish and Caenorhabditis elegans have shown that JIP3 promotes dynein-mediated retrograde transport to clear some organelles (lysosomes, early endosomes, and Golgi) from axons and prevent their potentially harmful accumulation in presynaptic regions. A JIP3 mutant suppressor screen in C. elegans revealed that JIP3 promotes the clearance of organelles from axons by blocking the action of the CSS system ((C) under bar dk5, (S) under bar AD Kinase, (S) under bar YD-2/Liprin). A synthesis of results in vertebrates with the new findings suggests that JIP3 blocks the CSS system from disrupting the connection between dynein and organelles. Most components of the CSS system are enriched at presynaptic active zones where they normally contribute to maintaining optimal levels of captured synaptic and dense core vesicles, in part by inhibiting dynein transport. The JIP3-CSS system model explains how neurons selectively regulate a single minus-end motor to exclude specific classes of organelles from axons, while at the same time ensuring optimal levels of synaptic and dense core vesicles.
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