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Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo

Alcadein α (Alcα) is a major cargo of kinesin-1 that is subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located in its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) motifs of the kinesin light chain (KLC), which act...

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Autores principales: Sobu, Yuriko, Furukori, Keiko, Chiba, Kyoko, Nairn, Angus C., Kinjo, Masataka, Hata, Saori, Suzuki, Toshiharu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739299/
https://www.ncbi.nlm.nih.gov/pubmed/29093024
http://dx.doi.org/10.1091/mbc.E17-05-0301
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author Sobu, Yuriko
Furukori, Keiko
Chiba, Kyoko
Nairn, Angus C.
Kinjo, Masataka
Hata, Saori
Suzuki, Toshiharu
author_facet Sobu, Yuriko
Furukori, Keiko
Chiba, Kyoko
Nairn, Angus C.
Kinjo, Masataka
Hata, Saori
Suzuki, Toshiharu
author_sort Sobu, Yuriko
collection PubMed
description Alcadein α (Alcα) is a major cargo of kinesin-1 that is subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located in its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) motifs of the kinesin light chain (KLC), which activate kinesin-1 and recruit kinesin-1 to Alcα cargo. We found that phosphorylation of three serine residues in the acidic region located between the two WD motifs is required for interaction with KLC. Phosphorylation of these serine residues may alter the disordered structure of the acidic region to induce direct association with KLC. Replacement of these serines with Ala results in a mutant that is unable to bind kinesin-1, which impairs exit of Alcα cargo from the Golgi. Despite this deficiency, the compromised Alcα mutant was still transported, albeit improperly by vesicles following missorting of the Alcα mutant with amyloid β-protein precursor (APP) cargo. This suggests that APP partially compensates for defective Alcα in anterograde transport by providing an alternative cargo receptor for kinesin-1.
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spelling pubmed-57392992018-03-02 Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo Sobu, Yuriko Furukori, Keiko Chiba, Kyoko Nairn, Angus C. Kinjo, Masataka Hata, Saori Suzuki, Toshiharu Mol Biol Cell Articles Alcadein α (Alcα) is a major cargo of kinesin-1 that is subjected to anterograde transport in neuronal axons. Two tryptophan- and aspartic acid-containing (WD) motifs located in its cytoplasmic domain directly bind the tetratricopeptide repeat (TPR) motifs of the kinesin light chain (KLC), which activate kinesin-1 and recruit kinesin-1 to Alcα cargo. We found that phosphorylation of three serine residues in the acidic region located between the two WD motifs is required for interaction with KLC. Phosphorylation of these serine residues may alter the disordered structure of the acidic region to induce direct association with KLC. Replacement of these serines with Ala results in a mutant that is unable to bind kinesin-1, which impairs exit of Alcα cargo from the Golgi. Despite this deficiency, the compromised Alcα mutant was still transported, albeit improperly by vesicles following missorting of the Alcα mutant with amyloid β-protein precursor (APP) cargo. This suggests that APP partially compensates for defective Alcα in anterograde transport by providing an alternative cargo receptor for kinesin-1. The American Society for Cell Biology 2017-12-15 /pmc/articles/PMC5739299/ /pubmed/29093024 http://dx.doi.org/10.1091/mbc.E17-05-0301 Text en © 2017 Sobu 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
Sobu, Yuriko
Furukori, Keiko
Chiba, Kyoko
Nairn, Angus C.
Kinjo, Masataka
Hata, Saori
Suzuki, Toshiharu
Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo
title Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo
title_full Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo
title_fullStr Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo
title_full_unstemmed Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo
title_short Phosphorylation of multiple sites within an acidic region of Alcadein α is required for kinesin-1 association and Golgi exit of Alcadein α cargo
title_sort phosphorylation of multiple sites within an acidic region of alcadein α is required for kinesin-1 association and golgi exit of alcadein α cargo
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739299/
https://www.ncbi.nlm.nih.gov/pubmed/29093024
http://dx.doi.org/10.1091/mbc.E17-05-0301
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