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Crohn's disease risk variant in GPR65 alters lysosomal function

ABSTRACT: Using an siRNA screen we identify a role for GPR65 in the defense against intracellular pathogens. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria as well as an accumulation of aberrant phagosomes and lysosomes. Transcriptional profiling revealed changes in genes associated with lysosomal function. Bone marrow-derived macrophages from WT or Gpr65-/- mice were harvested for RNA analysis.

ORGANISM(S): Mus musculus

SUBMITTER: Ramnik Xavier

PROVIDER: E-GEOD-69445 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Genetic Coding Variant in GPR65 Alters Lysosomal pH and Links Lysosomal Dysfunction with Colitis Risk.

Lassen Kara G KG McKenzie Craig I CI Mari Muriel M Murano Tatsuro T Begun Jakob J Baxt Leigh A LA Goel Gautam G Villablanca Eduardo J EJ Kuo Szu-Yu SY Huang Hailiang H Macia Laurence L Bhan Atul K AK Batten Marcel M Daly Mark J MJ Reggiori Fulvio F Mackay Charles R CR Xavier Ramnik J RJ

Immunity 20160607 6

Although numerous polymorphisms have been associated with inflammatory bowel disease (IBD), identifying the function of these genetic factors has proved challenging. Here we identified a role for nine genes in IBD susceptibility loci in antibacterial autophagy and characterized a role for one of these genes, GPR65, in maintaining lysosome function. Mice lacking Gpr65, a proton-sensing G protein-coupled receptor, showed increased susceptibly to bacteria-induced colitis. Epithelial cells and macro ...[more]

PMID: 27287411

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Crohn's disease risk variant in GPR65 alters lysosomal function

Project description:Using an siRNA screen we identify a role for GPR65 in the defense against intracellular pathogens. Epithelial cells and macrophages lacking GPR65 exhibited impaired clearance of intracellular bacteria as well as an accumulation of aberrant phagosomes and lysosomes. Transcriptional profiling revealed changes in genes associated with lysosomal function.

2016-06-15 | GSE69445 | GEO

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