title: Discovery of a novel splice variant of Fcar (CD89) unravels sequence segments necessary for efficient secretion: A story of bad signal peptides and good ones that nevertheless do not make it.
abstract: The IgA receptor, Fcar (CD89) consists of 5 sequence segments: 2 segments (S1, S2) forming the potential signal peptide, 2 extracellular EC domains that include the IgA binding site, and the transmembrane and cytoplasmic tail (TM/C) region. Numerous Fcar splice variants have been reported with various combinations of the sequence segments mentioned above. Here, we report a novel splice variant termed variant APD isolated from a healthy volunteer that lacks only the IgA-binding EC1 domain. Despite possessing the complete signal peptide S1+S2, the variant APD is only found in the intracellular space whereas the wild-type variant 1 is efficiently secreted and variant 4 leaks to the extracellular space. Further mutational experiments involving signal peptide replacements, cleavage site modifications, and studies on alternative isoforms demonstrate that despite the completeness of the signal peptide motif, the presence of the EC1 domain is essential for efficient extracellular export.
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.
authors.forename: Wai-Heng
authors.initials: WH
authors.lastname: Lua
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.
authors.forename: Wei-Li
authors.initials: WL
authors.lastname: Ling
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.
authors.forename: Chinh Tran-To
authors.initials: CT
authors.lastname: Su
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.
authors.forename: Joshua Yi
authors.initials: JY
authors.lastname: Yeo
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.|b Department of Biological Sciences , National University of Singapore (NUS) , Singapore.|c School of Biological Sciences, Nanyang Technological University (NTU) , Singapore.
authors.forename: Chandra Shekhar
authors.initials: CS
authors.lastname: Verma
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.
authors.forename: Birgit
authors.initials: B
authors.lastname: Eisenhaber
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.|d School of Computer Engineering, Nanyang Technological University (NTU) , Singapore.
authors.forename: Frank
authors.initials: F
authors.lastname: Eisenhaber
authors.affiliation: a Bioinformatics Institute, Agency for Science, Technology, and Research (A*STAR) , Singapore.|e p53 Laboratory, Agency for Science, Technology, and Research (A*STAR) , Singapore.
authors.forename: Samuel Ken-En
authors.initials: SK
authors.lastname: Gan
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D000595:Amino Acid Sequence; D015703:Antigens, CD / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D005110:Extracellular Space / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D021382:Protein Sorting Signals / Q000235:genetics*; D021381:Protein Transport; D011961:Receptors, Fc / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D055571:Secretory Pathway; D017384:Sequence Deletion
chemical_list: D015703:Antigens, CD; C036832:Fc(alpha) receptor; D021382:Protein Sorting Signals; D011961:Receptors, Fc; D049452:Green Fluorescent Proteins
keywords: CD89; Fcar; IgA; extracellular localization; splice variants