Genotype-phenotype correlation in PEX5-deficient peroxisome biogenesis defective cell lines. Export

@article{citeulike:4483785, abstract = {Proteins destined for the peroxisomal matrix are targeted by virtue of a peroxisomal targeting sequence type 1 (PTS1) or type 2 (PTS2). In humans, targeting of either class of proteins relies on a cytosolic receptor protein encoded by the PEX5 gene. Alternative splicing of PEX5 results in two protein variants, PEX5S and PEX5L. PEX5S is exclusively involved in PTS1 protein import, whereas PEX5L mediates the import of both PTS1 and PTS2 proteins. Genetic complementation testing with over 500 different fibroblast cell lines from patients diagnosed with a peroxisome biogenesis disorder (PBD) identified 11 cell lines with a defect in PEX5. The aim of this study was to characterize these cell lines at a biochemical and genetic level. To this end, the cultured fibroblasts were analyzed for very long chain fatty acid (VLCFA) concentrations, peroxisomal beta-and alpha-oxidation, dihydroxyacetone-phosphate acyltransferase (DHAPAT) activity, peroxisomal thiolase, and catalase immunofluorescence. Mutation analysis of the PEX5 gene revealed 11 different mutations, eight of which are novel. PTS1- and PTS2-protein import capacity was assessed by transfection of the cells with green fluorescent protein (GFP) tagged with either PTS1 or PTS2. Six cell lines showed a defect in both PTS1 and PTS2 protein import, whereas four cell lines only showed a defect in PTS1 protein import. The location of the different mutations within the PEX5 amino acid sequence correlates rather well with the peroxisomal protein import defect observed in the cell lines.}, author = {Ebberink, M. S. and Mooyer, P. A. and Koster, J. and Dekker, C. J. and Eyskens, F. J. and Dionisi-Vici, C. and Clayton, P. T. and Barth, P. G. and Wanders, R. J. and Waterham, H. R.}, citeulike-article-id = {4483785}, citeulike-linkout-0 = {http://dx.doi.org/10.1002/humu.20833}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18712838}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18712838}, doi = {10.1002/humu.20833}, issn = {1098-1004}, journal = {Human mutation}, keywords = {pex5}, month = {January}, number = {1}, pages = {93--98}, posted-at = {2009-05-07 03:12:59}, priority = {2}, title = {Genotype-phenotype correlation in PEX5-deficient peroxisome biogenesis defective cell lines.}, url = {http://dx.doi.org/10.1002/humu.20833}, volume = {30}, year = {2009} }

TY - JOUR ID - citeulike:4483785 L3 - citeulike-article-id:4483785 N2 - Proteins destined for the peroxisomal matrix are targeted by virtue of a peroxisomal targeting sequence type 1 (PTS1) or type 2 (PTS2). In humans, targeting of either class of proteins relies on a cytosolic receptor protein encoded by the PEX5 gene. Alternative splicing of PEX5 results in two protein variants, PEX5S and PEX5L. PEX5S is exclusively involved in PTS1 protein import, whereas PEX5L mediates the import of both PTS1 and PTS2 proteins. Genetic complementation testing with over 500 different fibroblast cell lines from patients diagnosed with a peroxisome biogenesis disorder (PBD) identified 11 cell lines with a defect in PEX5. The aim of this study was to characterize these cell lines at a biochemical and genetic level. To this end, the cultured fibroblasts were analyzed for very long chain fatty acid (VLCFA) concentrations, peroxisomal beta-and alpha-oxidation, dihydroxyacetone-phosphate acyltransferase (DHAPAT) activity, peroxisomal thiolase, and catalase immunofluorescence. Mutation analysis of the PEX5 gene revealed 11 different mutations, eight of which are novel. PTS1- and PTS2-protein import capacity was assessed by transfection of the cells with green fluorescent protein (GFP) tagged with either PTS1 or PTS2. Six cell lines showed a defect in both PTS1 and PTS2 protein import, whereas four cell lines only showed a defect in PTS1 protein import. The location of the different mutations within the PEX5 amino acid sequence correlates rather well with the peroxisomal protein import defect observed in the cell lines. IS - 1 JF - Human mutation SN - 1098-1004 EP - 98 TI - Genotype-phenotype correlation in PEX5-deficient peroxisome biogenesis defective cell lines. VL - 30 SP - 93 KW - pex5 AU - Ebberink, MS AU - Mooyer, PA AU - Koster, J AU - Dekker, CJ AU - Eyskens, FJ AU - Dionisi-Vici, C AU - Clayton, PT AU - Barth, PG AU - Wanders, RJ AU - Waterham, HR PY - 2009/01// UR - http://dx.doi.org/10.1002/humu.20833 ER -