title: FCRLA is a resident endoplasmic reticulum protein that associates with intracellular Igs, IgM, IgG and IgA.
abstract: Fc receptor-like A (FCRLA) is an unusual member of the extended Fc receptor family. FCRLA has homology to receptors for the Fc portion of Ig (FCR) and to other FCRL proteins. However, unlike these other family representatives, which are typically transmembrane receptors with extracellular ligand-binding domains, FCRLA has no predicted transmembrane domain or N-linked glycosylation sites and is an intracellular protein. We show by confocal microscopy and biochemical assays that FCRLA is a soluble resident endoplasmic reticulum (ER) protein, but it does not possess the amino acid sequence KDEL as an ER retention motif in its C-terminus. Using a series of deletion mutants, we found that its ER retention is most likely mediated by the amino terminal partial Ig-like domain. We have identified ER-localized Ig as the FCRLA ligand. FCRLA is unique among the large family of Fc receptors, in that it is capable of associating with multiple Ig isotypes, IgM, IgG and IgA. Among hemopoietic cells, FCRLA expression is restricted to the B lineage and is most abundant in germinal center B lymphocytes. The studies reported here demonstrate that FCRLA is more broadly expressed among human B lineage cells than originally reported; it is found at significant levels in resting blood B cells and at varying levels in all B-cell subsets in tonsil.
authors.affiliation: Department of Microbiology, University of Alabama at Birmingham, UAB 406 SHEL, 1530 Third Avenue South, Birmingham, AL 35294, USA.
authors.forename: Teresa
authors.initials: T
authors.lastname: Santiago
authors.forename: Sergei V
authors.initials: SV
authors.lastname: Kulemzin
authors.forename: Evdokia S
authors.initials: ES
authors.lastname: Reshetnikova
authors.forename: Nikolai A
authors.initials: NA
authors.lastname: Chikaev
authors.forename: Olga Y
authors.initials: OY
authors.lastname: Volkova
authors.forename: Ludmila V
authors.initials: LV
authors.lastname: Mechetina
authors.forename: Meina
authors.initials: M
authors.lastname: Zhao
authors.forename: Randall S
authors.initials: RS
authors.lastname: Davis
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Taranin
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Najakshin
authors.forename: Linda M
authors.initials: LM
authors.lastname: Hendershot
authors.forename: Peter D
authors.initials: PD
authors.lastname: Burrows
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology*; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000276:immunology*; D006367:HeLa Cells; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology
chemical_list: C452186:FCRLA protein, human; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D011961:Receptors, Fc; D011971:Receptors, Immunologic