title: Complement activation by ceramide transporter proteins.
abstract: C1q is the initiator of the classical complement pathway and, as such, is essential for efficient opsonization and clearance of pathogens, altered self-structures, and apoptotic cells. The ceramide transporter protein (CERT) and its longer splicing isoform CERTL are known to interact with extracellular matrix components, such as type IV collagen, and with the innate immune protein serum amyloid P. In this article, we report a novel function of CERT in the innate immune response. Both CERT isoforms, when immobilized, were found to bind the globular head region of C1q and to initiate the classical complement pathway, leading to activation of C4 and C3, as well as generation of the membrane attack complex C5b-9. In addition, C1q was shown to bind to endogenous CERTL on the surface of apoptotic cells. These results demonstrate the role of CERTs in innate immunity, especially in the clearance of apoptotic cells.
authors.affiliation: Division of Neuroscience, School for Mental Health and Neuroscience, Faculty of Health, Medicine, and Life Sciences, Maastricht University, 6200 MD Maastricht, The Netherlands;
authors.forename: Gerard H
authors.initials: GH
authors.lastname: Bode
authors.forename: Mario
authors.initials: M
authors.lastname: Losen
authors.forename: Wim A
authors.initials: WA
authors.lastname: Buurman
authors.forename: Robert
authors.initials: R
authors.lastname: Veerhuis
authors.forename: Peter C
authors.initials: PC
authors.lastname: Molenaar
authors.forename: Harry W M
authors.initials: HW
authors.lastname: Steinbusch
authors.forename: Marc H
authors.initials: MH
authors.lastname: De Baets
authors.forename: Mohamed R
authors.initials: MR
authors.lastname: Daha
authors.forename: Pilar
authors.initials: P
authors.lastname: Martinez-Martinez
mesh_terms: D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001665:Binding Sites; D015922:Complement C1q / Q000276:immunology / Q000378:metabolism*; D003170:Complement Pathway, Alternative / Q000187:drug effects; D003171:Complement Pathway, Classical / Q000187:drug effects; D006801:Humans; D007113:Immunity, Innate; D019169:Jurkat Cells; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020033:Protein Isoforms / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology / Q000502:physiology*; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D000683:Serum Amyloid P-Component / Q000502:physiology
chemical_list: D000911:Antibodies, Monoclonal; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D000683:Serum Amyloid P-Component; D015922:Complement C1q; C119090:CERT1 protein, human; D017346:Protein Serine-Threonine Kinases