title: Characterization of human FCRLA isoforms.
abstract: FCRLA is an ER-resident B-cell specific protein. The exact function of this protein remains unclear although human FCRLA has been recently shown to interact with IgM, IgG and IgA. The retention of FCRLA in ER is mediated by the N-terminal domain. The major human FCRLA isoform is encoded by five exons, of which one encodes a short signal peptide (SSP) and the others code four protein domains. Here we show that human tissues also produce transcripts which contain an additional exon and encode proteins with signal peptide that is six residues longer (LSP). Transfection experiments demonstrated that the extension of the signal peptide had no visible effect on the topology and molecular mass of the processed four-domain FCRLA isoform. However, the length of the signal peptide was found to affect processing of two-domain FCRLA isoforms composed of the third and fourth domains (FCRLAd2). The signal peptide was not cleaved in the SSP-FCRLAd2 and this isoform was found to accumulate in the ER. In contrast, the LSP-containing FCRLAd2 isoform was processed, O-glycosylated and secreted. The secreted FCRLAd2 isoform did not interact with IgG- or IgM-immunosorbents.
authors.affiliation: Institute of Molecular and Cellular Biology SB RAS, 8 Lavrentiev Avenue, Novosibirsk 630090, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Kulemzin
authors.forename: Nikolai
authors.initials: N
authors.lastname: Chikaev
authors.forename: Olga
authors.initials: O
authors.lastname: Volkova
authors.forename: Evdokiya
authors.initials: E
authors.lastname: Reshetnikova
authors.forename: Alexander
authors.initials: A
authors.lastname: Taranin
authors.forename: Alexander
authors.initials: A
authors.lastname: Najakshin
authors.forename: Ludmila
authors.initials: L
authors.lastname: Mechetina
mesh_terms: D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008969:Molecular Sequence Data; D020033:Protein Isoforms / Q000235:genetics* / Q000378:metabolism; D021382:Protein Sorting Signals / Q000235:genetics*; D011961:Receptors, Fc; D011971:Receptors, Immunologic / Q000235:genetics* / Q000378:metabolism
chemical_list: C452186:FCRLA protein, human; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D020033:Protein Isoforms; D021382:Protein Sorting Signals; D011961:Receptors, Fc; D011971:Receptors, Immunologic
keywords: B lymphocyte; ER; FCRLA; FcR-like; Isoform; LSP; SP; SSP; Signal peptide; endoplasmic reticulum; long signal peptide; short signal peptide; signal peptide