Identification of secreted CD155 isoforms q B eatrice Baury, a Damien Masson, a Brian M. McDermott Jr., b Anne Jarry, a Herv e M. Blotti  ere, a Philippe Blanchardie, c Christian L. Laboisse, a Patrick Lustenberger, c Vincent R. Racaniello, b and Marc G. Denis a, * a Institut National de la Sant e et de la Recherche M edicale U539, Facult e de M edecine, 1 rue Gaston Veil, 44035 Nantes, France b Department of Microbiology, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA c Laboratoire de Biochimie, Facult e de M edecine, 1 rue Gaston Veil, 44035 Nantes, France Received 1 August 2003 Abstract The CD155 gene is a member of the immunoglobulin superfamily. We first demonstrate the existence of soluble CD155 (sCD155) isoforms in culture medium conditioned by CD155-expressing cells, in human serum and in cerebrospinal fluid. sCD155 concen- tration was measured in human serum and cerebrospinal fluid using a specific ELISA. Analysis of conditioned media indicated that sCD155 release does not require protease activity. In order to determine which tissues are responsible for sCD155 expression, we have quantified CD155 mRNAs in human normal tissues. The highest expression was observed in liver. The CD155a transcript is the most abundant and the proportion of the CD155b and CD155c variants was similar between the tissues. Finally, serum purified sCD155 reduces poliovirus entry mediated by membrane-bound CD155. The high level of CD155 synthesis in many tissues and the presence of sCD155 in biological fluids suggest the existence of an important role for the protein in cellular function. Ó 2003 Elsevier Inc. All rights reserved. Keywords: CD155; Poliovirus receptor; Immunoglobulin superfamilly; Soluble forms; Splicing The CD155 protein (or human poliovirus receptor, PVR) is a highly glycosylated 70-kDa type Ia single pass transmembrane cell surface protein. The CD155 gene was isolated based on its ability to mediate the attachment of poliovirus to host cells [1]. The CD155 protein is a member of the immunoglobulin superfamily. Its extracellular region contains three immunoglobulin- like domains: an outermost V-like domain followed by two C2-like domains [1]. The CD155 gene belongs to a subgroup of the immunoglobulin superfamily sharing the general extracellular structure V-C2-C2. This sub- group includes murine and monkey homologues of CD155 [2,3], the rat Tage4 gene, identified as a tumor antigen overexpressed in rat colon carcinomas [4,5] and also as the rat homologue of CD155 [6]. Four additional members first named Poliovirus Receptor Related (PRR), then nectin 1, 2, 3, and 4 [7–9], also belong to this subgroup of molecules. Members of the immunoglobulin superfamily have a diversity of functions, but in most cases the common denominator is of a recognition role at the cell surface. Most of these proteins are involved in cell–cell interac- tion during normal or pathological processes. A number of these membrane proteins have soluble forms that are released into the extracellular space. Most soluble pro- teins are generated by proteolytic cleavage at the cell surface by “sheddases,” matrix metalloproteinases or members of the ADAM (a desintegrin and metallopro- teinase) family. The cleavage occurs close to the trans- membrane domain releasing a nearly intact extracellular domain with binding activity. Ectodomain shedding has been reported for a number of members of the immu- noglobulin superfamily including, for instance, the vas- cular cell membrane adhesion molecule VCAM-1/ Biochemical and Biophysical Research Communications 309 (2003) 175–182 www.elsevier.com/locate/ybbrc BBRC q Abbreviations: PVR, poliovirus receptor; PRR, Poliovirus Re- ceptor Related; ADAM, a desintegrin and metalloproteinase; VCAM- 1, vascular cell membrane adhesion molecule; ICAM-1, intercellular adhesion molecule; CEA, carcinoembryonic antigen; ELISA, enzyme- linked immunosorbent assay; KIM-1, kidney injury molecule-1. * Corresponding author. Fax: +33-2-40-08-41-14. E-mail address: mdenis@nantes.inserm.fr (M.G. Denis). 0006-291X/$ - see front matter Ó 2003 Elsevier Inc. All rights reserved. doi:10.1016/S0006-291X(03)01560-2