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Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon
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...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2018
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232961/ https://www.ncbi.nlm.nih.gov/pubmed/29949458 http://dx.doi.org/10.1091/mbc.E18-01-0007 |
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author | Shi, Liang Hines, Timothy Bergson, Clare Smith, Deanna |
author_facet | Shi, Liang Hines, Timothy Bergson, Clare Smith, Deanna |
author_sort | Shi, Liang |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6232961 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-62329612018-11-20 Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon Shi, Liang Hines, Timothy Bergson, Clare Smith, Deanna Mol Biol Cell Articles 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. The American Society for Cell Biology 2018-08-15 /pmc/articles/PMC6232961/ /pubmed/29949458 http://dx.doi.org/10.1091/mbc.E18-01-0007 Text en © 2018 Shi et al. “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. http://creativecommons.org/licenses/by-nc-sa/3.0 This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License. |
spellingShingle | Articles Shi, Liang Hines, Timothy Bergson, Clare Smith, Deanna Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon |
title | Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon |
title_full | Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon |
title_fullStr | Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon |
title_full_unstemmed | Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon |
title_short | Coupling of microtubule motors with AP-3 generated organelles in axons by NEEP21 family member calcyon |
title_sort | coupling of microtubule motors with ap-3 generated organelles in axons by neep21 family member calcyon |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6232961/ https://www.ncbi.nlm.nih.gov/pubmed/29949458 http://dx.doi.org/10.1091/mbc.E18-01-0007 |
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