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Article: gC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection

TitlegC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infection
Authors
Issue Date2001
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/IMR
Citation
Immunological Reviews, 2001, v. 180, p. 65-77 How to Cite?
AbstractHuman gC1q-R (p33, p32, C1qBP, TAP) is a ubiquitously expressed, multiligand-binding, multicompartmental cellular protein involved in various ligand-mediated cellular responses. Although expressed on the surface of cells, an intriguing feature of the membrane-associated form of gC1q-R is that its translated amino acid sequence does not predict the presence of either a sequence motif compatible with a transmembrane segment or a consensus site for a glycosylphosphatidylinositol anchor. Moreover, the N-terminal sequence of the pre-pro-protein of gC1q-R contains a motif that targets the molecule to the mitochondria and as such was deemed unlikely to be expressed on the surface. However, several lines of experimental evidence dearly show that gC1q-R is present in all compartments of the cell, including the extracellular cell surface. First, surface labeling of B lymphocytes with the membrane-impermeable reagent sulfosuccinimidyl 6-(biotinamido)hexanoate shows specific biotin incorporation into the surface-expressed but not the intracellular form of gC1q-R. Second, FACS and confocal laser scanning microscopic analyses using anti-gC1q-R IgG mAb 60.11 or 74.5.2, and the fluorophore Alexa 488-conjugated F(ab′) 2 goat anti-mouse IgG as a probe, demonstrated specific staining of Raji cells (>95% viable). Three-dimensional analyses of the same cells by confocal microscopy showed staining distribution that was consistent with surface expression. Third, endothelial gC1q-R, which is associated with the urokinase plasminogen activator receptor, and cytokeratin 1 bind 125I-high molecular weight kininogen in a specific manner, and the binding is inhibited dose-dependently by mAb 74.5.2 recognizing gC1q-R residues 204-218. Fourth, native gC1q-R purified from Raji cell membranes but not intracellular gC1q-R is glycosylated, as evidenced by a positive periodic acid Schiff stain as well as sensitivity to digestion with endoglycosidase H and F. Finally, cross-linking experiments using C1q as a ligand indicate that both cC1q-R and gC1q-R are co-immunoprecipitated with anti-C1q. Taken together, the evidence accumulated to date supports the concept that in addition to its intracellular localization, gC1q-R is expressed on the cell surface and can serve as a binding site for plasma and microbial proteins, but also challenges the existing paradigm that mitochondrial proteins never leave their designated compartment. It is therefore proposed that gC1q-R belongs to a growing list of a class of proteins initially targeted to the mitochondria but then exported to different compartments of the cell through specific mechanisms which have yet to be identified. The designation 'multifunctional and multicompartmental cellular proteins' is proposed for this class of proteins.
Persistent Identifierhttp://hdl.handle.net/10722/178739
ISSN
2015 Impact Factor: 9.542
2015 SCImago Journal Rankings: 7.059
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorGhebrehiwet, Ben_US
dc.contributor.authorLim, BLen_US
dc.contributor.authorKumar, Ren_US
dc.contributor.authorFeng, Xen_US
dc.contributor.authorPeerschke, EIBen_US
dc.date.accessioned2012-12-19T09:49:25Z-
dc.date.available2012-12-19T09:49:25Z-
dc.date.issued2001en_US
dc.identifier.citationImmunological Reviews, 2001, v. 180, p. 65-77en_US
dc.identifier.issn0105-2896en_US
dc.identifier.urihttp://hdl.handle.net/10722/178739-
dc.description.abstractHuman gC1q-R (p33, p32, C1qBP, TAP) is a ubiquitously expressed, multiligand-binding, multicompartmental cellular protein involved in various ligand-mediated cellular responses. Although expressed on the surface of cells, an intriguing feature of the membrane-associated form of gC1q-R is that its translated amino acid sequence does not predict the presence of either a sequence motif compatible with a transmembrane segment or a consensus site for a glycosylphosphatidylinositol anchor. Moreover, the N-terminal sequence of the pre-pro-protein of gC1q-R contains a motif that targets the molecule to the mitochondria and as such was deemed unlikely to be expressed on the surface. However, several lines of experimental evidence dearly show that gC1q-R is present in all compartments of the cell, including the extracellular cell surface. First, surface labeling of B lymphocytes with the membrane-impermeable reagent sulfosuccinimidyl 6-(biotinamido)hexanoate shows specific biotin incorporation into the surface-expressed but not the intracellular form of gC1q-R. Second, FACS and confocal laser scanning microscopic analyses using anti-gC1q-R IgG mAb 60.11 or 74.5.2, and the fluorophore Alexa 488-conjugated F(ab′) 2 goat anti-mouse IgG as a probe, demonstrated specific staining of Raji cells (>95% viable). Three-dimensional analyses of the same cells by confocal microscopy showed staining distribution that was consistent with surface expression. Third, endothelial gC1q-R, which is associated with the urokinase plasminogen activator receptor, and cytokeratin 1 bind 125I-high molecular weight kininogen in a specific manner, and the binding is inhibited dose-dependently by mAb 74.5.2 recognizing gC1q-R residues 204-218. Fourth, native gC1q-R purified from Raji cell membranes but not intracellular gC1q-R is glycosylated, as evidenced by a positive periodic acid Schiff stain as well as sensitivity to digestion with endoglycosidase H and F. Finally, cross-linking experiments using C1q as a ligand indicate that both cC1q-R and gC1q-R are co-immunoprecipitated with anti-C1q. Taken together, the evidence accumulated to date supports the concept that in addition to its intracellular localization, gC1q-R is expressed on the cell surface and can serve as a binding site for plasma and microbial proteins, but also challenges the existing paradigm that mitochondrial proteins never leave their designated compartment. It is therefore proposed that gC1q-R belongs to a growing list of a class of proteins initially targeted to the mitochondria but then exported to different compartments of the cell through specific mechanisms which have yet to be identified. The designation 'multifunctional and multicompartmental cellular proteins' is proposed for this class of proteins.en_US
dc.languageengen_US
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/IMRen_US
dc.relation.ispartofImmunological Reviewsen_US
dc.subject.meshAmino Acid Motifsen_US
dc.subject.meshAnimalsen_US
dc.subject.meshAntigens, Cd44en_US
dc.subject.meshBacterial Proteinsen_US
dc.subject.meshBlood Platelets - Metabolismen_US
dc.subject.meshBlood Proteins - Metabolismen_US
dc.subject.meshCarrier Proteinsen_US
dc.subject.meshCell Compartmentationen_US
dc.subject.meshCell Membrane - Metabolismen_US
dc.subject.meshChemotaxisen_US
dc.subject.meshChromosomes, Human, Pair 17 - Geneticsen_US
dc.subject.meshComplement C1q - Metabolismen_US
dc.subject.meshFlow Cytometryen_US
dc.subject.meshGene Expression Regulationen_US
dc.subject.meshGenesen_US
dc.subject.meshHumansen_US
dc.subject.meshInfection - Metabolismen_US
dc.subject.meshInflammation - Metabolismen_US
dc.subject.meshKininogen, High-Molecular-Weight - Metabolismen_US
dc.subject.meshLigandsen_US
dc.subject.meshLymphocyte Activationen_US
dc.subject.meshMembrane Glycoproteinsen_US
dc.subject.meshMembrane Proteins - Metabolismen_US
dc.subject.meshMiceen_US
dc.subject.meshMicroscopy, Confocalen_US
dc.subject.meshMitochondria - Metabolismen_US
dc.subject.meshMitochondrial Proteinsen_US
dc.subject.meshNeoplasm Proteins - Physiologyen_US
dc.subject.meshPhagocytosisen_US
dc.subject.meshRatsen_US
dc.subject.meshReceptors, Complement - Chemistry - Genetics - Immunology - Physiologyen_US
dc.subject.meshSignal Transductionen_US
dc.subject.meshStaphylococcal Protein A - Metabolismen_US
dc.subject.meshStructure-Activity Relationshipen_US
dc.subject.meshSubcellular Fractions - Metabolismen_US
dc.subject.meshTumor Cells, Cultureden_US
dc.subject.meshViral Proteins - Metabolismen_US
dc.subject.meshVitronectin - Metabolismen_US
dc.titlegC1q-R/p33, a member of a new class of multifunctional and multicompartmental cellular proteins, is involved in inflammation and infectionen_US
dc.typeArticleen_US
dc.identifier.emailLim, BL: bllim@hkucc.hku.hken_US
dc.identifier.authorityLim, BL=rp00744en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1034/j.1600-065X.2001.1800106.xen_US
dc.identifier.pmid11414365-
dc.identifier.scopuseid_2-s2.0-0034997841en_US
dc.identifier.hkuros57874-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034997841&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume180en_US
dc.identifier.spage65en_US
dc.identifier.epage77en_US
dc.identifier.isiWOS:000169079000006-
dc.publisher.placeDenmarken_US
dc.identifier.scopusauthoridGhebrehiwet, B=7005039582en_US
dc.identifier.scopusauthoridLim, BL=7201983917en_US
dc.identifier.scopusauthoridKumar, R=36014147800en_US
dc.identifier.scopusauthoridFeng, X=35073844100en_US
dc.identifier.scopusauthoridPeerschke, EIB=7005991940en_US

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