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Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1

Neurons are highly polarized cells having distinct somatodendritic and axonal domains. Here we report that polarized sorting of the Cu(2+) transporter ATP7B and the vesicle-SNARE VAMP4 to the somatodendritic domain of rat hippocampal neurons is mediated by recognition of dileucine-based signals in t...

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Autores principales: Jain, Shweta, Farías, Ginny G., Bonifacino, Juan S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294670/
https://www.ncbi.nlm.nih.gov/pubmed/25378584
http://dx.doi.org/10.1091/mbc.E14-07-1177
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author Jain, Shweta
Farías, Ginny G.
Bonifacino, Juan S.
author_facet Jain, Shweta
Farías, Ginny G.
Bonifacino, Juan S.
author_sort Jain, Shweta
collection PubMed
description Neurons are highly polarized cells having distinct somatodendritic and axonal domains. Here we report that polarized sorting of the Cu(2+) transporter ATP7B and the vesicle-SNARE VAMP4 to the somatodendritic domain of rat hippocampal neurons is mediated by recognition of dileucine-based signals in the cytosolic domains of the proteins by the σ1 subunit of the clathrin adaptor AP-1. Under basal Cu(2+) conditions, ATP7B was localized to the trans-Golgi network (TGN) and the plasma membrane of the soma and dendrites but not the axon. Mutation of a dileucine-based signal in ATP7B or overexpression of a dominant-negative σ1 mutant resulted in nonpolarized distribution of ATP7B between the somatodendritic and axonal domains. Furthermore, addition of high Cu(2+) concentrations, previously shown to reduce ATP7B incorporation into AP-1–containing clathrin-coated vesicles, caused loss of TGN localization and somatodendritic polarity of ATP7B. These findings support the notion of AP-1 as an effector of polarized sorting in neurons and suggest that altered polarity of ATP7B in polarized cell types might contribute to abnormal copper metabolism in the MEDNIK syndrome, a neurocutaneous disorder caused by mutations in the σ1A subunit isoform of AP-1.
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spelling pubmed-42946702015-03-30 Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1 Jain, Shweta Farías, Ginny G. Bonifacino, Juan S. Mol Biol Cell Articles Neurons are highly polarized cells having distinct somatodendritic and axonal domains. Here we report that polarized sorting of the Cu(2+) transporter ATP7B and the vesicle-SNARE VAMP4 to the somatodendritic domain of rat hippocampal neurons is mediated by recognition of dileucine-based signals in the cytosolic domains of the proteins by the σ1 subunit of the clathrin adaptor AP-1. Under basal Cu(2+) conditions, ATP7B was localized to the trans-Golgi network (TGN) and the plasma membrane of the soma and dendrites but not the axon. Mutation of a dileucine-based signal in ATP7B or overexpression of a dominant-negative σ1 mutant resulted in nonpolarized distribution of ATP7B between the somatodendritic and axonal domains. Furthermore, addition of high Cu(2+) concentrations, previously shown to reduce ATP7B incorporation into AP-1–containing clathrin-coated vesicles, caused loss of TGN localization and somatodendritic polarity of ATP7B. These findings support the notion of AP-1 as an effector of polarized sorting in neurons and suggest that altered polarity of ATP7B in polarized cell types might contribute to abnormal copper metabolism in the MEDNIK syndrome, a neurocutaneous disorder caused by mutations in the σ1A subunit isoform of AP-1. The American Society for Cell Biology 2015-01-15 /pmc/articles/PMC4294670/ /pubmed/25378584 http://dx.doi.org/10.1091/mbc.E14-07-1177 Text en © 2015 Jain et al. 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 (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Jain, Shweta
Farías, Ginny G.
Bonifacino, Juan S.
Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
title Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
title_full Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
title_fullStr Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
title_full_unstemmed Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
title_short Polarized sorting of the copper transporter ATP7B in neurons mediated by recognition of a dileucine signal by AP-1
title_sort polarized sorting of the copper transporter atp7b in neurons mediated by recognition of a dileucine signal by ap-1
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4294670/
https://www.ncbi.nlm.nih.gov/pubmed/25378584
http://dx.doi.org/10.1091/mbc.E14-07-1177
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