Molecular and functional characterization of Mouse S5D-SRCRB, a new member of the group B scavenger receptor cysteine-rich superfamily

Autor: Miró-Julià, Cristina, Roselló, Sandra, Martínez, Vanesa G., Fink, Dorte R., Escoda-Ferrán, Cristina, Padilla, Olga, Vázquez-Echevarría, Citlali, Espinal-Marin, Paula, Pujades, Cristina, García-Pardo, Angeles, Vila, Jordi, Serra-Pagès, Carles, Holmskov, Uffe, Yélamos, José, Lozano, Francisco
Rok vydání: 2011
Zdroj: Digital.CSIC. Repositorio Institucional del CSIC
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Popis: 12 páginas, 8 figuras -- PAGS nros. 2344-2354
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
This work was supported by grants from the Spanish Ministry of Education (SAF 2007-62197 to F.L.), the Generalitat de Catalunya (Grants 2009/SGR/524 to J.Y. and 2009/SGR/252 to F.L.), and the Spanish Research Network on Infectious Diseases (Red Espan˜ola de Investigacio´n en Patologı´a Infecciosa, RD06/0008/1013 to F.L.). C.M.-J. and C.E.-F. are recipients of fellowships from the Spanish Ministry of Education (FPU AP2007-02223 and FPI BES2008-005544, respectively).
Databáze: OpenAIRE
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