Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping

Kamran Rizzolo; Jennifer Huen; Ashwani Kumar; Sadhna Phanse; James Vlasblom; Yoshito Kakihara; Hussein A. Zeineddine; Zoran Minic; Jamie Snider; Wen Wang; Carles Pons; Thiago V. Seraphim; Edgar Erik Boczek; Simon Alberti; Michael Costanzo; Chad L. Myers; Igor Stagljar; Charles Boone; Mohan Babu; Walid A. Houry

doi:10.1016/j.celrep.2017.08.074

Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping

Kamran Rizzolo, Jennifer Huen, Ashwani Kumar, Sadhna Phanse, James Vlasblom, Yoshito Kakihara, Hussein A. Zeineddine, Zoran Minic, Jamie Snider, Wen Wang, Carles Pons, Thiago V. Seraphim, Edgar Erik Boczek, Simon Alberti, Michael Costanzo, Chad L. Myers, Igor Stagljar, Charles Boone, Mohan Babu, Walid A. Houry

Computer Science and Engineering

Research output: Contribution to journal › Article › peer-review

40 Scopus citations

Abstract

A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps. We further found that many chaperones interact with proteins that form foci or condensates under stress conditions. Using an in vitro reconstitution approach, we demonstrate condensate formation for the highly conserved AAA+ ATPases Rvb1 and Rvb2, which are part of the R2TP complex that interacts with Hsp90. This expanded view of the chaperone network in the cell clearly demonstrates the distinction between chaperones having broad versus narrow substrate specificities in protein homeostasis.

Original language	English (US)
Pages (from-to)	2735-2748
Number of pages	14
Journal	Cell reports
Volume	20
Issue number	11
DOIs	https://doi.org/10.1016/j.celrep.2017.08.074
State	Published - Sep 12 2017

Bibliographical note

Funding Information:
We thank Dr. Craig Smibert (University of Toronto) for the pRS116 DHH1 plasmid, Dr. Judith Frydman (Stanford University) for pESC GFP-VHL plasmid, Dr. Guri Giaever (University of British Columbia) for the RVB1/rvb1 Δ and RVB2/rvb2 Δ diploid strains, and Dr. Grant Brown (University of Toronto) for the NUP49-mCHERRY strain. K.R. was supported by a Canadian Institutes of Health Research (CIHR) Training Program in Protein Folding and Interaction Dynamics: Principles and Diseases fellowship and by a University of Toronto Fellowship from the Department of Biochemistry. J.H. was supported by a Natural Sciences and Engineering Research Council of Canada PGSD2 fellowship. T.V.S. was supported by a CNPq-Brazil fellowship ( 202192/2015-6 ) and a Saskatchewan Health Research Foundation postdoctoral fellowship. M.B. holds a CIHR New Investigator award. C.B. and C.L.M. are fellows of the Canadian Institute for Advanced Research (CIFAR) . This work was partially supported by the National Institutes of Health ( R01HG005853 to CB and CLM and R01HG005084 to CLM). This work was also supported by CIHR (RSN-124512, MOP-125952, RSN-132191, and FDN-154318 to M.B., MOP-93778 to W.A.H., and MOP-81256 to I.S. and W.A.H.).

Publisher Copyright:
© 2017 The Author(s)

Keywords

Hsp90
NAJ chaperone complex
R2TP
Rvb1
Rvb2
chaperone network
genetic interaction profiles
genetic interactions
perinuclear condensate
physical interactions

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Rizzolo, K., Huen, J., Kumar, A., Phanse, S., Vlasblom, J., Kakihara, Y., Zeineddine, H. A., Minic, Z., Snider, J., Wang, W., Pons, C., Seraphim, T. V., Boczek, E. E., Alberti, S., Costanzo, M., Myers, C. L., Stagljar, I., Boone, C., Babu, M., & Houry, W. A. (2017). Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping. Cell reports, 20(11), 2735-2748. https://doi.org/10.1016/j.celrep.2017.08.074

Rizzolo, K, Huen, J, Kumar, A, Phanse, S, Vlasblom, J, Kakihara, Y, Zeineddine, HA, Minic, Z, Snider, J, Wang, W, Pons, C, Seraphim, TV, Boczek, EE, Alberti, S, Costanzo, M, Myers, CL, Stagljar, I, Boone, C, Babu, M & Houry, WA 2017, 'Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping', Cell reports, vol. 20, no. 11, pp. 2735-2748. https://doi.org/10.1016/j.celrep.2017.08.074

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abstract = "A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps. We further found that many chaperones interact with proteins that form foci or condensates under stress conditions. Using an in vitro reconstitution approach, we demonstrate condensate formation for the highly conserved AAA+ ATPases Rvb1 and Rvb2, which are part of the R2TP complex that interacts with Hsp90. This expanded view of the chaperone network in the cell clearly demonstrates the distinction between chaperones having broad versus narrow substrate specificities in protein homeostasis.",

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author = "Kamran Rizzolo and Jennifer Huen and Ashwani Kumar and Sadhna Phanse and James Vlasblom and Yoshito Kakihara and Zeineddine, {Hussein A.} and Zoran Minic and Jamie Snider and Wen Wang and Carles Pons and Seraphim, {Thiago V.} and Boczek, {Edgar Erik} and Simon Alberti and Michael Costanzo and Myers, {Chad L.} and Igor Stagljar and Charles Boone and Mohan Babu and Houry, {Walid A.}",

note = "Funding Information: We thank Dr. Craig Smibert (University of Toronto) for the pRS116 DHH1 plasmid, Dr. Judith Frydman (Stanford University) for pESC GFP-VHL plasmid, Dr. Guri Giaever (University of British Columbia) for the RVB1/rvb1 Δ and RVB2/rvb2 Δ diploid strains, and Dr. Grant Brown (University of Toronto) for the NUP49-mCHERRY strain. K.R. was supported by a Canadian Institutes of Health Research (CIHR) Training Program in Protein Folding and Interaction Dynamics: Principles and Diseases fellowship and by a University of Toronto Fellowship from the Department of Biochemistry. J.H. was supported by a Natural Sciences and Engineering Research Council of Canada PGSD2 fellowship. T.V.S. was supported by a CNPq-Brazil fellowship ( 202192/2015-6 ) and a Saskatchewan Health Research Foundation postdoctoral fellowship. M.B. holds a CIHR New Investigator award. C.B. and C.L.M. are fellows of the Canadian Institute for Advanced Research (CIFAR) . This work was partially supported by the National Institutes of Health ( R01HG005853 to CB and CLM and R01HG005084 to CLM). This work was also supported by CIHR (RSN-124512, MOP-125952, RSN-132191, and FDN-154318 to M.B., MOP-93778 to W.A.H., and MOP-81256 to I.S. and W.A.H.). Publisher Copyright: {\textcopyright} 2017 The Author(s)",

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AU - Rizzolo, Kamran

AU - Huen, Jennifer

AU - Kumar, Ashwani

AU - Phanse, Sadhna

AU - Vlasblom, James

AU - Kakihara, Yoshito

AU - Zeineddine, Hussein A.

AU - Minic, Zoran

AU - Snider, Jamie

AU - Wang, Wen

AU - Pons, Carles

AU - Seraphim, Thiago V.

AU - Boczek, Edgar Erik

AU - Alberti, Simon

AU - Costanzo, Michael

AU - Myers, Chad L.

AU - Stagljar, Igor

AU - Boone, Charles

AU - Babu, Mohan

AU - Houry, Walid A.

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N2 - A comprehensive view of molecular chaperone function in the cell was obtained through a systematic global integrative network approach based on physical (protein-protein) and genetic (gene-gene or epistatic) interaction mapping. This allowed us to decipher interactions involving all core chaperones (67) and cochaperones (15) of Saccharomyces cerevisiae. Our analysis revealed the presence of a large chaperone functional supercomplex, which we named the naturally joined (NAJ) chaperone complex, encompassing Hsp40, Hsp70, Hsp90, AAA+, CCT, and small Hsps. We further found that many chaperones interact with proteins that form foci or condensates under stress conditions. Using an in vitro reconstitution approach, we demonstrate condensate formation for the highly conserved AAA+ ATPases Rvb1 and Rvb2, which are part of the R2TP complex that interacts with Hsp90. This expanded view of the chaperone network in the cell clearly demonstrates the distinction between chaperones having broad versus narrow substrate specificities in protein homeostasis.

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Features of the Chaperone Cellular Network Revealed through Systematic Interaction Mapping

Abstract

Bibliographical note

Keywords

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