Mapping the interactome of a major mammalian endoplasmic reticulum heat shock protein 90

Feng Hong, Saleh Mohammad Rachidi, Debbie Lundgren, David Han, Xiu Huang, Hongyu Zhao, Yayoi Kimura, Hisashi Hirano, Osamu Ohara, Heiichiro Udono, Songdong Meng, Bei Liu, Zihai Li

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11 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number0169260
JournalPLoS One
Volume12
Issue number1
DOIs
Publication statusPublished - Jan 1 2017

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ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Hong, F., Rachidi, S. M., Lundgren, D., Han, D., Huang, X., Zhao, H., Kimura, Y., Hirano, H., Ohara, O., Udono, H., Meng, S., Liu, B., & Li, Z. (2017). Mapping the interactome of a major mammalian endoplasmic reticulum heat shock protein 90. PLoS One, 12(1), [0169260]. https://doi.org/10.1371/journal.pone.0169260