title: Goodpasture antigen-binding protein is a soluble exportable protein that interacts with type IV collagen. Identification of novel membrane-bound isoforms.
abstract: Goodpasture-antigen binding protein (GPBP) is a nonconventional Ser/Thr kinase for basement membrane type IV collagen. Various studies have questioned these findings and proposed that GPBP serves as transporter of ceramide between the endoplasmic reticulum and the Golgi apparatus. Here we show that cells expressed at least two GPBP isoforms resulting from canonical (77-kDa) and noncanonical (91-kDa) mRNA translation initiation. The 77-kDa polypeptide interacted with type IV collagen and localized as a soluble form in the extracellular compartment. The 91-kDa polypeptide and its derived 120-kDa polypeptide associated with cellular membranes and regulated the extracellular levels of the 77-kDa polypeptide. A short motif containing two phenylalanines in an acidic tract and the 26-residue Ser-rich region were required for efficient 77-kDa polypeptide secretion. Removal of the 26-residue Ser-rich region by alternative exon splicing rendered the protein cytosolic and sensitive to the reduction of sphingomyelin cellular levels. These and previous data implicate GPBPs in a multicompartmental program for protein secretion (i.e. type IV collagen) that includes: 1) phosphorylation and regulation of protein molecular/supramolecular organization and 2) interorganelle ceramide trafficking and regulation of protein cargo transport to the plasma membrane.
authors.affiliation: Centro de Investigación Príncipe Felipe, 46012 Valencia, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Revert
authors.forename: Ignacio
authors.initials: I
authors.lastname: Ventura
authors.forename: Pilar
authors.initials: P
authors.lastname: Martínez-Martínez
authors.forename: Froilán
authors.initials: F
authors.lastname: Granero-Moltó
authors.forename: Francisco
authors.initials: F
authors.lastname: Revert-Ros
authors.forename: Jesús
authors.initials: J
authors.lastname: Macías
authors.forename: Juan
authors.initials: J
authors.lastname: Saus
mesh_terms: D000143:Acids / Q000737:chemistry; D002462:Cell Membrane / Q000378:metabolism; D024141:Collagen Type IV / Q000737:chemistry*; D005091:Exons; D006056:Golgi Apparatus / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008954:Models, Biological; D010649:Phenylalanine / Q000737:chemistry; D011485:Protein Binding; D020033:Protein Isoforms; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000502:physiology*; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000143:Acids; D024141:Collagen Type IV; D020033:Protein Isoforms; D012333:RNA, Messenger; D010649:Phenylalanine; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases
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