Nature Genetics
9, 115 - 125 (1995)
doi:10.1038/ng0295-115
Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disordersGabriele Dodt1, 2, Nancy Braverman3, Candice Wong1, 2, Ann Moser1, Hugo W. Moser1, 4, Paul Watkins4, David Valle3, 5
& Stephen J. Gould1, 2, 6
1The Kennedy Krieger Research Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
2Departments of Cell Biology and Anatomy, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
3Departments of Pediatrics, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
4Departments of Neurology, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
5Departments of Howard Hughes Medical Institute, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
6present address: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA Correspondence should be addressed to S.J.G. The peroxisome biogenesis disorders (PBDs) are lethal recessive diseases caused by defects in peroxisome assembly. We have isolated PXR1, a human homologue of the yeast P. pastoris PAS8 (peroxisome assembly) gene. PXR1, like PAS8, encodes a receptor for proteins with the type−1 peroxisomal targeting signal (PTS1). Mutations in PXR1 define complementation group 2 of PBDs and expression of PXR1 rescues the PTS1 import defect of fibroblasts from these patients. Based on the observation that PXR1 exists both in the cytosol and in association with peroxisomes, we propose that PXR1 protein recognizes PTS1 −containing proteins in the cytosol and directs them to the peroxisome.
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