Accounting for protein subcellular localization: A compartmental map of the rat liver proteome

Michel Jadot, Marielle Boonen, Jacqueline Thirion, Nan Wang, Jinchuan Xing, Caifeng Zhao, Abla Tannous, Meiqian Qian, Haiyan Zheng, John K Everett, Dirk F Moore, David E Sleat, Peter Lobel

Research output: Contribution to journalArticle

Abstract

Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle while a significant fraction may reside elsewhere. As a step towards a comprehensive cellular map, we used subcellular fractionation with classic balance sheet analysis and isobaric labeling/quantitative mass spectrometry to assign locations to >6000 rat liver proteins. We provide quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments: nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, Golgi, plasma membrane and cytosol. Accounting for total intracellular distribution improves quality of organelle assignments and assigns proteins with multiple locations. Protein assignments and supporting data are available online through the Prolocate website (http://prolocate.cabm.rutgers.edu). As an example of the utility of this dataset, we have used organelle assignments to help analyze whole exome sequencing data from an infant dying at six months of age from a suspected neurodegenerative lysosomal storage disorder of unknown etiology. Sequencing data was prioritized using lists of lysosomal proteins comprising well-established residents of this organelle as well as novel candidates identified in this study. The latter included copper transporter 1, encoded by SLC31A1, which we localized to both the plasma membrane and lysosome. The patient harbors two predicted loss of function mutations in SLC31A1, suggesting that this may represent a heretofore undescribed recessive lysosomal storage disease gene.

LanguageEnglish
JournalMolecular & cellular proteomics : MCP
DOIs
Publication statusE-pub ahead of print - 2016

Fingerprint

Proteome
Liver
Rats
Organelles
Proteins
Cell membranes
Lysosomes
Cell Membrane
Lysosomal Storage Diseases
Exome
Mitochondria
Peroxisomes
Metabolic Diseases
Fractionation
Ports and harbors
Metabolic Networks and Pathways
Endoplasmic Reticulum
Cytosol
Labeling
Mass spectrometry

Cite this

Jadot, Michel ; Boonen, Marielle ; Thirion, Jacqueline ; Wang, Nan ; Xing, Jinchuan ; Zhao, Caifeng ; Tannous, Abla ; Qian, Meiqian ; Zheng, Haiyan ; Everett, John K ; Moore, Dirk F ; Sleat, David E ; Lobel, Peter. / Accounting for protein subcellular localization : A compartmental map of the rat liver proteome. In: Molecular & cellular proteomics : MCP. 2016.
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Accounting for protein subcellular localization : A compartmental map of the rat liver proteome. / Jadot, Michel; Boonen, Marielle; Thirion, Jacqueline; Wang, Nan; Xing, Jinchuan; Zhao, Caifeng; Tannous, Abla; Qian, Meiqian; Zheng, Haiyan; Everett, John K; Moore, Dirk F; Sleat, David E; Lobel, Peter.

In: Molecular & cellular proteomics : MCP, 2016.

Research output: Contribution to journalArticle

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T1 - Accounting for protein subcellular localization

T2 - Molecular and Cellular Proteomics

AU - Jadot, Michel

AU - Boonen, Marielle

AU - Thirion, Jacqueline

AU - Wang, Nan

AU - Xing, Jinchuan

AU - Zhao, Caifeng

AU - Tannous, Abla

AU - Qian, Meiqian

AU - Zheng, Haiyan

AU - Everett, John K

AU - Moore, Dirk F

AU - Sleat, David E

AU - Lobel, Peter

N1 - Copyright © 2016, The American Society for Biochemistry and Molecular Biology.

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N2 - Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle while a significant fraction may reside elsewhere. As a step towards a comprehensive cellular map, we used subcellular fractionation with classic balance sheet analysis and isobaric labeling/quantitative mass spectrometry to assign locations to >6000 rat liver proteins. We provide quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments: nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, Golgi, plasma membrane and cytosol. Accounting for total intracellular distribution improves quality of organelle assignments and assigns proteins with multiple locations. Protein assignments and supporting data are available online through the Prolocate website (http://prolocate.cabm.rutgers.edu). As an example of the utility of this dataset, we have used organelle assignments to help analyze whole exome sequencing data from an infant dying at six months of age from a suspected neurodegenerative lysosomal storage disorder of unknown etiology. Sequencing data was prioritized using lists of lysosomal proteins comprising well-established residents of this organelle as well as novel candidates identified in this study. The latter included copper transporter 1, encoded by SLC31A1, which we localized to both the plasma membrane and lysosome. The patient harbors two predicted loss of function mutations in SLC31A1, suggesting that this may represent a heretofore undescribed recessive lysosomal storage disease gene.

AB - Accurate knowledge of the intracellular location of proteins is important for numerous areas of biomedical research including assessing fidelity of putative protein-protein interactions, modeling cellular processes at a system-wide level and investigating metabolic and disease pathways. Many proteins have not been localized, or have been incompletely localized, partly because most studies do not account for entire subcellular distribution. Thus, proteins are frequently assigned to one organelle while a significant fraction may reside elsewhere. As a step towards a comprehensive cellular map, we used subcellular fractionation with classic balance sheet analysis and isobaric labeling/quantitative mass spectrometry to assign locations to >6000 rat liver proteins. We provide quantitative data and error estimates describing the distribution of each protein among the eight major cellular compartments: nucleus, mitochondria, lysosomes, peroxisomes, endoplasmic reticulum, Golgi, plasma membrane and cytosol. Accounting for total intracellular distribution improves quality of organelle assignments and assigns proteins with multiple locations. Protein assignments and supporting data are available online through the Prolocate website (http://prolocate.cabm.rutgers.edu). As an example of the utility of this dataset, we have used organelle assignments to help analyze whole exome sequencing data from an infant dying at six months of age from a suspected neurodegenerative lysosomal storage disorder of unknown etiology. Sequencing data was prioritized using lists of lysosomal proteins comprising well-established residents of this organelle as well as novel candidates identified in this study. The latter included copper transporter 1, encoded by SLC31A1, which we localized to both the plasma membrane and lysosome. The patient harbors two predicted loss of function mutations in SLC31A1, suggesting that this may represent a heretofore undescribed recessive lysosomal storage disease gene.

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DO - 10.1074/mcp.M116.064527

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JF - Molecular and Cellular Proteomics

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