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Keeping Neuronal Cargoes on the Right Track: New Insights into Regulators of Axonal Transport
- Source :
- The Neuroscientist. 23:232-250
- Publication Year :
- 2016
- Publisher :
- SAGE Publications, 2016.
-
Abstract
- 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 (Cdk5, SAD Kinase, SYD-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.
- Subjects :
- Neurons
0301 basic medicine
Endosome
General Neuroscience
Cyclin-dependent kinase 5
Dynein
Biology
Golgi apparatus
Axonal Transport
Cell biology
03 medical and health sciences
symbols.namesake
030104 developmental biology
Microtubule
Organelle
Axoplasmic transport
symbols
Animals
Humans
Neurology (clinical)
Active zone
Subjects
Details
- ISSN :
- 10894098 and 10738584
- Volume :
- 23
- Database :
- OpenAIRE
- Journal :
- The Neuroscientist
- Accession number :
- edsair.doi.dedup.....8f895ed8a680e4c39c3fa9040a916517