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

Liang Shi, Timothy Hines, Clare Bergson, Deanna Smith

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2055-2068
Number of pages14
JournalMolecular Biology of the Cell
Volume29
Issue number17
DOIs
StatePublished - Aug 15 2018

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Microtubules
Organelles
Axons
Endosomes
Lysosomes
Capsid Proteins
Proteins
Dyneins
Dacarbazine
Axonal Transport
Transcription Factor AP-1
Brain
Spinal Ganglia
Organelle Biogenesis
RNA Interference
Neurodegenerative Diseases
calcyon
Neurons
Red DND-99

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon. / Shi, Liang; Hines, Timothy; Bergson, Clare; Smith, Deanna.

In: Molecular Biology of the Cell, Vol. 29, No. 17, 15.08.2018, p. 2055-2068.

Research output: Contribution to journalArticle

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