RESUMO
CDHR3 (cadherin-related family member 3) is a transmembrane protein that is highly expressed in airway epithelia and the only known receptor for rhinovirus C (RV-C). A CDHR3 SNP (rs6967330) with G to A base change has been linked to severe exacerbations of asthma and increased susceptibility to RV-C infections in young children. The goals of this study were to determine the subcellular localization of CDHR3 and to test the hypothesis that CDHR3 asthma-risk genotype affects epithelial cell function and susceptibility to RV-C infections of the airway epithelia. We used immunofluorescence imaging, Western blot analysis, and transmission electron microscopy to show CDHR3 subcellular localization in apical cells, including expression in the cilia of airway epithelia. Polymorphisms in CDHR3 rs6967330 locus (GâA) that were previously associated with childhood asthma were related to differences in CDHR3 expression and epithelial cell function. The rs6967330 A allele was associated with higher overall protein expression and RV-C binding and replication compared with the rs6967330 G allele. Furthermore, the rs6967330 A allele was associated with earlier ciliogenesis and higher FOXJ1 expression. Finally, CDHR3 genotype had no significant effects on membrane integrity or ciliary beat function. These findings provide information on the subcellular localization and possible functions of CDHR3 in the airways and link CDHR3 asthma-risk genotype to increased RV-C binding and replication.
Assuntos
Caderinas/genética , Células Epiteliais/virologia , Proteínas de Membrana/genética , Infecções por Picornaviridae/genética , Polimorfismo de Nucleotídeo Único , Mucosa Respiratória/patologia , Rhinovirus/fisiologia , Alelos , Asma/complicações , Asma/genética , Brônquios/patologia , Proteínas Relacionadas a Caderinas , Caderinas/fisiologia , Cílios/química , Células Epiteliais/química , Células Epiteliais/ultraestrutura , Predisposição Genética para Doença , Genótipo , Humanos , Proteínas de Membrana/fisiologia , Infecções por Picornaviridae/virologia , Mucosa Respiratória/virologia , Frações Subcelulares/químicaRESUMO
The original version of the Data Descriptor contained errors in the author list and affiliations. Rita Leite's first name was misspelled as "Rite" and affiliations 4 and 5 were incorrectly swapped. In addition, members of the March of Dimes Prematurity Research Center consortium were not listed in the agreed positions within the author list. These errors have now been corrected in the HTML and PDF versions.