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dc.contributor.authorWeekes, M
dc.contributor.authorAntrobus, R
dc.contributor.authorTalbot, S
dc.contributor.authorHör, S
dc.contributor.authorSimecek, N
dc.contributor.authorSmith, Duncan L
dc.contributor.authorBloor, S
dc.contributor.authorRandow, F
dc.contributor.authorLehner, P
dc.date.accessioned2012-05-25T16:10:09Z
dc.date.available2012-05-25T16:10:09Z
dc.date.issued2012-03-02
dc.identifier.citationProteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6. 2012, 11 (3):1475-84 J Proteome Resen_GB
dc.identifier.issn1535-3907
dc.identifier.pmid22292497
dc.identifier.doi10.1021/pr201135e
dc.identifier.urihttp://hdl.handle.net/10541/226052
dc.description.abstractThe endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins. To identify a more comprehensive repertoire of proteins whose cell surface expression is dependent on gp96, we developed plasma membrane profiling (PMP), a technique that combines SILAC labeling with selective cell surface aminooxy-biotinylation. This approach allowed us to compare the relative abundance of plasma membrane (PM) proteins on gp96-deficient versus gp96-reconstituted murine pre-B cells. Analysis of unfractionated tryptic peptides initially identified 113 PM proteins, which extended to 706 PM proteins using peptide prefractionation. We confirmed a requirement for gp96 in the cell surface expression of certain TLRs and integrins and found a marked decrease in cell surface expression of four members of the extended LDL receptor family (LDLR, LRP6, Sorl1 and LRP8) in the absence of gp96. Other novel gp96 client proteins included CD180/Ly86, important in the B-cell response to lipopolysaccharide. We highlight common structural motifs in these client proteins that may be recognized by gp96, including the beta-propeller and leucine-rich repeat. This study therefore identifies the extended LDL receptor family as an important new family of proteins whose cell surface expression is regulated by gp96.
dc.language.isoenen
dc.rightsArchived with thanks to Journal of proteome researchen_GB
dc.titleProteomic plasma membrane profiling reveals an essential role for gp96 in the cell surface expression of LDLR family members, including the LDL receptor and LRP6.en
dc.typeArticleen
dc.contributor.departmentCambridge Institute for Medical Research, University of Cambridge , Hills Road, Cambridge, CB2 0XY, United Kingdom.en_GB
dc.identifier.journalJournal of Proteome Researchen_GB
html.description.abstractThe endoplasmic reticulum chaperone gp96 is required for the cell surface expression of a narrow range of proteins, including toll-like receptors (TLRs) and integrins. To identify a more comprehensive repertoire of proteins whose cell surface expression is dependent on gp96, we developed plasma membrane profiling (PMP), a technique that combines SILAC labeling with selective cell surface aminooxy-biotinylation. This approach allowed us to compare the relative abundance of plasma membrane (PM) proteins on gp96-deficient versus gp96-reconstituted murine pre-B cells. Analysis of unfractionated tryptic peptides initially identified 113 PM proteins, which extended to 706 PM proteins using peptide prefractionation. We confirmed a requirement for gp96 in the cell surface expression of certain TLRs and integrins and found a marked decrease in cell surface expression of four members of the extended LDL receptor family (LDLR, LRP6, Sorl1 and LRP8) in the absence of gp96. Other novel gp96 client proteins included CD180/Ly86, important in the B-cell response to lipopolysaccharide. We highlight common structural motifs in these client proteins that may be recognized by gp96, including the beta-propeller and leucine-rich repeat. This study therefore identifies the extended LDL receptor family as an important new family of proteins whose cell surface expression is regulated by gp96.


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