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Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90

Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have co...

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Autores principales: Hong, Feng, Mohammad Rachidi, Saleh, Lundgren, Debbie, Han, David, Huang, Xiu, Zhao, Hongyu, Kimura, Yayoi, Hirano, Hisashi, Ohara, Osamu, Udono, Heichiiro, Meng, Songdong, Liu, Bei, Li, Zihai
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215799/
https://www.ncbi.nlm.nih.gov/pubmed/28056051
http://dx.doi.org/10.1371/journal.pone.0169260
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author Hong, Feng
Mohammad Rachidi, Saleh
Lundgren, Debbie
Han, David
Huang, Xiu
Zhao, Hongyu
Kimura, Yayoi
Hirano, Hisashi
Ohara, Osamu
Udono, Heichiiro
Meng, Songdong
Liu, Bei
Li, Zihai
author_facet Hong, Feng
Mohammad Rachidi, Saleh
Lundgren, Debbie
Han, David
Huang, Xiu
Zhao, Hongyu
Kimura, Yayoi
Hirano, Hisashi
Ohara, Osamu
Udono, Heichiiro
Meng, Songdong
Liu, Bei
Li, Zihai
author_sort Hong, Feng
collection PubMed
description Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins were reduced in gp96 knockdown cells, compared to levels observed in wild type cells. By immunoprecipitation, we found that 201 proteins associated with gp96. Gene Ontology analysis indicated that these proteins are involved in metabolism, transport, translation, protein folding, development, localization, response to stress and cellular component biogenesis. While known gp96 clients such as integrins, Toll-like receptors (TLRs) and Wnt co-receptor LRP6, were confirmed, cell surface HSP receptor CD91, TLR4 pathway protein CD180, WDR1, GANAB and CAPZB were identified as potentially novel substrates of gp96. Taken together, our study establishes gp96 as a critical chaperone to integrate innate immunity, Wnt signaling and organ development.
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spelling pubmed-52157992017-01-19 Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90 Hong, Feng Mohammad Rachidi, Saleh Lundgren, Debbie Han, David Huang, Xiu Zhao, Hongyu Kimura, Yayoi Hirano, Hisashi Ohara, Osamu Udono, Heichiiro Meng, Songdong Liu, Bei Li, Zihai PLoS One Research Article Up to 10% of cytosolic proteins are dependent on the mammalian heat shock protein 90 (HSP90) for folding. However, the interactors of its endoplasmic reticulum (ER) paralogue (gp96, Grp94 and HSP90b1) has not been systematically identified. By combining genetic and biochemical approaches, we have comprehensively mapped the interactome of gp96 in macrophages and B cells. A total of 511 proteins were reduced in gp96 knockdown cells, compared to levels observed in wild type cells. By immunoprecipitation, we found that 201 proteins associated with gp96. Gene Ontology analysis indicated that these proteins are involved in metabolism, transport, translation, protein folding, development, localization, response to stress and cellular component biogenesis. While known gp96 clients such as integrins, Toll-like receptors (TLRs) and Wnt co-receptor LRP6, were confirmed, cell surface HSP receptor CD91, TLR4 pathway protein CD180, WDR1, GANAB and CAPZB were identified as potentially novel substrates of gp96. Taken together, our study establishes gp96 as a critical chaperone to integrate innate immunity, Wnt signaling and organ development. Public Library of Science 2017-01-05 /pmc/articles/PMC5215799/ /pubmed/28056051 http://dx.doi.org/10.1371/journal.pone.0169260 Text en © 2017 Hong et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Hong, Feng
Mohammad Rachidi, Saleh
Lundgren, Debbie
Han, David
Huang, Xiu
Zhao, Hongyu
Kimura, Yayoi
Hirano, Hisashi
Ohara, Osamu
Udono, Heichiiro
Meng, Songdong
Liu, Bei
Li, Zihai
Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90
title Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90
title_full Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90
title_fullStr Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90
title_full_unstemmed Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90
title_short Mapping the Interactome of a Major Mammalian Endoplasmic Reticulum Heat Shock Protein 90
title_sort mapping the interactome of a major mammalian endoplasmic reticulum heat shock protein 90
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215799/
https://www.ncbi.nlm.nih.gov/pubmed/28056051
http://dx.doi.org/10.1371/journal.pone.0169260
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