title: Molecular and functional characterization of mouse S5D-SRCRB: a new group B member of the scavenger receptor cysteine-rich superfamily.
abstract: The scavenger receptor cysteine-rich superfamily (SRCR-SF) members are transmembrane and/or secreted receptors exhibiting one or several repeats of a cysteine-rich protein module of ∼100 aa, named scavenger receptor cysteine-rich (SRCR). Two types of SRCR domains (A or B) have been reported, which differ in the number of coding exons and intradomain cysteines. Although no unifying function has been reported for SRCR-SF members, recognition of pathogen-associated molecular patterns (PAMPs) was recently shown for some of them. In this article, we report the structural and functional characterization of mouse S5D-SRCRB, a new group B member of the SRCR-SF. The s5d-srcrb gene maps at mouse chromosome 7 and encompasses 14 exons extending over 15 kb. The longest cDNA sequence found is 4286 bp in length and encodes a mature protein of 1371 aa, with a predicted M(r) of 144.6 kDa. Using an episomal mammalian-expression system, a glycosylated soluble recombinant form >200 kDa was obtained and used as immunogen for the generation of specific rat mAbs. Subsequent immunohistochemical and real-time PCR analysis showed significant S5D-SRCRB expression in murine genitourinary and digestive tracts. S5D-SRCRB was shown to bind endogenous extracellular matrix proteins (laminin and galectin-1), as well as PAMPs present on Gram-positive and Gram-negative bacteria and fungi. PAMP binding by S5D-SRCRB induced microbial aggregation and subsequent inhibition of PAMP-induced cytokine release. These abilities suggest that S5D-SRCRB might play a role in the innate defense and homeostasis of certain specialized epithelial surfaces.
authors.affiliation: Centre Esther Koplowitz, Fundació Clínic per a la Recerca Biomèdica, 08036 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Miró-Julià
authors.forename: Sandra
authors.initials: S
authors.lastname: Roselló
authors.forename: Vanesa G
authors.initials: VG
authors.lastname: Martínez
authors.forename: Dorte R
authors.initials: DR
authors.lastname: Fink
authors.forename: Cristina
authors.initials: C
authors.lastname: Escoda-Ferran
authors.forename: Olga
authors.initials: O
authors.lastname: Padilla
authors.forename: Citlali
authors.initials: C
authors.lastname: Vázquez-Echeverría
authors.forename: Paula
authors.initials: P
authors.lastname: Espinal-Marin
authors.forename: Cristina
authors.initials: C
authors.lastname: Pujades
authors.forename: Angeles
authors.initials: A
authors.lastname: García-Pardo
authors.forename: Jordi
authors.initials: J
authors.lastname: Vila
authors.forename: Carles
authors.initials: C
authors.lastname: Serra-Pagès
authors.forename: Uffe
authors.initials: U
authors.lastname: Holmskov
authors.forename: José
authors.initials: J
authors.lastname: Yélamos
authors.forename: Francisco
authors.initials: F
authors.lastname: Lozano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D003545:Cysteine / Q000378:metabolism*; D004847:Epithelial Cells / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D005786:Gene Expression Regulation / Q000276:immunology*; D057809:HEK293 Cells; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology*; D011485:Protein Binding / Q000276:immunology; D017434:Protein Structure, Tertiary / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D051192:Receptors, Pattern Recognition / Q000737:chemistry / Q000378:metabolism / Q000502:physiology; D051122:Scavenger Receptors, Class B / Q000096:biosynthesis / Q000737:chemistry* / Q000235:genetics / Q000502:physiology*
chemical_list: D051192:Receptors, Pattern Recognition; C557499:S5D-SRCRB protein, mouse; C543737:SSc5D protein, human; D051122:Scavenger Receptors, Class B; D003545:Cysteine