RGD Reference Report - Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon. - Rat Genome Database

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

Authors: Shi, Liang  Hines, Timothy  Bergson, Clare  Smith, Deanna 
Citation: Shi L, etal., Mol Biol Cell. 2018 Aug 15;29(17):2055-2068. doi: 10.1091/mbc.E18-01-0007. Epub 2018 Jun 27.
RGD ID: 15097509
Pubmed: (View Article at PubMed) PMID:29949458
DOI: Full-text: DOI:10.1091/mbc.E18-01-0007

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.

Gene Ontology Annotations    

Biological Process

Cellular Component
axon  (IDA)

Objects Annotated

Genes (Rattus norvegicus)
Caly  (calcyon neuron-specific vesicular protein)

Additional Information