Format

Send to

Choose Destination
Mol Biol Cell. 2018 Aug 15;29(17):2055-2068. doi: 10.1091/mbc.E18-01-0007. Epub 2018 Jun 27.

Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon.

Author information

1
Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta University, Augusta, GA 30912.
2
Department of Biological Sciences, University of South Carolina, Columbia, SC 29208.

Abstract

Transport of late endosomes and lysosome-related organelles (LE/LROs) in axons is essential for supplying synaptic cargoes and for removing damaged macromolecules. Defects in this system are implicated in a range of human neurodegenerative and neurodevelopmental disorders. The findings reported here identify a novel mechanism regulating LE/LRO transport based on the coordinated coupling of microtubule motors and vesicle coat proteins to the neuron-enriched, transmembrane protein calcyon (Caly). We found that the cytoplasmic C-terminus of Caly pulled down proteins involved in microtubule-dependent transport (DIC, KIF5A, p150Glued, Lis1) and organelle biogenesis (AP-1 and AP-3) from the brain. In addition, RNA interference-mediated knockdown of Caly increased the percentage of static LE/LROs labeled by LysoTracker in cultured dorsal root ganglion axons. In contrast, overexpression of Caly stimulated movement of organelles positive for LysoTracker or the AP-3 cargo GFP-PI4KIIα. However, a Caly mutant (ATEA) that does not bind AP-3 was unable to pull down motor proteins from brain, and expression of the ATEA mutant failed to increase either LE/LRO flux or levels of associated dynein. Taken together, these data support the hypothesis that Caly is a multifunctional scaffolding protein that regulates axonal transport of LE/LROs by coordinately interacting with motor and vesicle coat proteins.

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center