title: Membrane protein 4F2/CD98 is a cell surface receptor involved in the internalization and trafficking of human β-Defensin 3 in epithelial cells.
abstract: Human β-defensins play a pivotal role in the innate immune response. Although expressed by and acting at epithelial surfaces, little is known about their specific interaction with epithelial structures. Here, we identify the transmembrane protein CD98 as a cell surface receptor involved in the internalization of human β-defensin 3 (hBD3) in human epithelial A549 cells. CD98 and hBD3 extensively colocalize on the basolateral domain of A549. While verifying their direct binding by fluorescence resonance energy transfer and surface plasmon resonance, we mapped the interaction to CD98 residues 304-414, i.e. to the region known to interact with the proteins of intestinal bacteria during colonic invasion. Treatment of A549 cells with hBD3 dramatically reduces CD98 expression and conversely, knockdown of CD98 expression impairs hBD3 cell surface binding and internalization. Competition for bacterial binding to CD98 and downregulation of CD98 expression may represent novel mechanisms for the antibacterial activity of hBD3.
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
authors: Irene
authors: I
authors: Colavita
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
authors: Ersilia
authors: E
authors: Nigro
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.
authors: Daniela
authors: D
authors: Sarnataro
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università degli Studi di Napoli Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.
authors: Olga
authors: O
authors: Scudiero
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
authors: Vincenzo
authors: V
authors: Granata
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy; Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Seconda Università degli Studi di Napoli, Via Vivaldi 43, 81100 Caserta, Italy.
authors: Aurora
authors: A
authors: Daniele
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy.
authors: Adriana
authors: A
authors: Zagari
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy; PeptiPharma, Viale Città D'Europa 679, 00144 Rome, Italy. Electronic address: a.pessi@peptipharma.it.
authors: Antonello
authors: A
authors: Pessi
authors: CEINGE-Biotecnologie Avanzate S.c.a r.l., Via Gaetano Salvatore 486, 80145 Naples, Italy; IRCCS-Fondazione SDN, Via Emanuele Gianturco 113, 80142 Naples, Italy. Electronic address: salvator@unina.it.
authors: Francesco
authors: F
authors: Salvatore
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D001710:Biotin / Q000737:chemistry; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D004926:Escherichia coli / Q000187:drug effects; D031541:Fluorescence Resonance Energy Transfer; D027261:Fusion Regulatory Protein-1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D018613:Microscopy, Confocal; D056004:Molecular Dynamics Simulation; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D040901:Proteomics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D020349:Surface Plasmon Resonance; D023083:beta-Defensins / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; C422950:DEFB103A protein, human; D027261:Fusion Regulatory Protein-1; D034741:RNA, Small Interfering; D023083:beta-Defensins; D001710:Biotin