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The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse

Dysbindin assembles into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with the adaptor protein complex 3 (AP-3), mediating a common endosome-trafficking route. Deficiencies in AP-3 and BLOC-1 affect synaptic vesicle composition. However, whether AP-3-BLOC-1–depen...

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Autores principales: Larimore, Jennifer, Tornieri, Karine, Ryder, Pearl V., Gokhale, Avanti, Zlatic, Stephanie A., Craige, Branch, Lee, Joshua D., Talbot, Konrad, Pare, Jean-Francois, Smith, Yoland, Faundez, Victor
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237628/
https://www.ncbi.nlm.nih.gov/pubmed/21998198
http://dx.doi.org/10.1091/mbc.E11-07-0592
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author Larimore, Jennifer
Tornieri, Karine
Ryder, Pearl V.
Gokhale, Avanti
Zlatic, Stephanie A.
Craige, Branch
Lee, Joshua D.
Talbot, Konrad
Pare, Jean-Francois
Smith, Yoland
Faundez, Victor
author_facet Larimore, Jennifer
Tornieri, Karine
Ryder, Pearl V.
Gokhale, Avanti
Zlatic, Stephanie A.
Craige, Branch
Lee, Joshua D.
Talbot, Konrad
Pare, Jean-Francois
Smith, Yoland
Faundez, Victor
author_sort Larimore, Jennifer
collection PubMed
description Dysbindin assembles into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with the adaptor protein complex 3 (AP-3), mediating a common endosome-trafficking route. Deficiencies in AP-3 and BLOC-1 affect synaptic vesicle composition. However, whether AP-3-BLOC-1–dependent sorting events that control synapse membrane protein content take place in cell bodies upstream of nerve terminals remains unknown. We tested this hypothesis by analyzing the targeting of phosphatidylinositol-4-kinase type II α (PI4KIIα), a membrane protein present in presynaptic and postsynaptic compartments. PI4KIIα copurified with BLOC-1 and AP-3 in neuronal cells. These interactions translated into a decreased PI4KIIα content in the dentate gyrus of dysbindin-null BLOC-1 deficiency and AP-3–null mice. Reduction of PI4KIIα in the dentate reflects a failure to traffic from the cell body. PI4KIIα was targeted to processes in wild-type primary cultured cortical neurons and PC12 cells but failed to reach neurites in cells lacking either AP-3 or BLOC-1. Similarly, disruption of an AP-3–sorting motif in PI4KIIα impaired its sorting into processes of PC12 and primary cultured cortical neuronal cells. Our findings indicate a novel vesicle transport mechanism requiring BLOC-1 and AP-3 complexes for cargo sorting from neuronal cell bodies to neurites and nerve terminals.
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spelling pubmed-32376282012-03-01 The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse Larimore, Jennifer Tornieri, Karine Ryder, Pearl V. Gokhale, Avanti Zlatic, Stephanie A. Craige, Branch Lee, Joshua D. Talbot, Konrad Pare, Jean-Francois Smith, Yoland Faundez, Victor Mol Biol Cell Articles Dysbindin assembles into the biogenesis of lysosome-related organelles complex 1 (BLOC-1), which interacts with the adaptor protein complex 3 (AP-3), mediating a common endosome-trafficking route. Deficiencies in AP-3 and BLOC-1 affect synaptic vesicle composition. However, whether AP-3-BLOC-1–dependent sorting events that control synapse membrane protein content take place in cell bodies upstream of nerve terminals remains unknown. We tested this hypothesis by analyzing the targeting of phosphatidylinositol-4-kinase type II α (PI4KIIα), a membrane protein present in presynaptic and postsynaptic compartments. PI4KIIα copurified with BLOC-1 and AP-3 in neuronal cells. These interactions translated into a decreased PI4KIIα content in the dentate gyrus of dysbindin-null BLOC-1 deficiency and AP-3–null mice. Reduction of PI4KIIα in the dentate reflects a failure to traffic from the cell body. PI4KIIα was targeted to processes in wild-type primary cultured cortical neurons and PC12 cells but failed to reach neurites in cells lacking either AP-3 or BLOC-1. Similarly, disruption of an AP-3–sorting motif in PI4KIIα impaired its sorting into processes of PC12 and primary cultured cortical neuronal cells. Our findings indicate a novel vesicle transport mechanism requiring BLOC-1 and AP-3 complexes for cargo sorting from neuronal cell bodies to neurites and nerve terminals. The American Society for Cell Biology 2011-12-15 /pmc/articles/PMC3237628/ /pubmed/21998198 http://dx.doi.org/10.1091/mbc.E11-07-0592 Text en © 2011 Larimore 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 of Cell Biology.
spellingShingle Articles
Larimore, Jennifer
Tornieri, Karine
Ryder, Pearl V.
Gokhale, Avanti
Zlatic, Stephanie A.
Craige, Branch
Lee, Joshua D.
Talbot, Konrad
Pare, Jean-Francois
Smith, Yoland
Faundez, Victor
The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse
title The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse
title_full The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse
title_fullStr The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse
title_full_unstemmed The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse
title_short The schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse
title_sort schizophrenia susceptibility factor dysbindin and its associated complex sort cargoes from cell bodies to the synapse
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3237628/
https://www.ncbi.nlm.nih.gov/pubmed/21998198
http://dx.doi.org/10.1091/mbc.E11-07-0592
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