Mutations in the PTS1 receptor gene, PXR1, define complementation group 2 of the peroxisome biogenesis disorders

Abstract

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.

Quantitative Analysis of Peroxisomal Protein Import in Vitro

“…In contrast, fibroblasts from patients with the fatal peroxisomal disorder cerebrohepatorenal (Zellweger) syndrome were incapable of importing significant amounts of biotinylated luciferase (ϳ4% of the A431 level). The cell line, called FAIR-T, is known to lack the PTS1 receptor, Pex5p [21,27].…”

Peroxisomes: simple in function but complex in maintenance

“…In 11 cases, the molecular basis for a peroxisomal disease could be related to a nonfunctional Pex protein. Rhizomelic chondrodysplasia punctata (pex7) and the cerebrohepatorenal syndrome of Zellweger (pex5) are typical examples of a new and surprising class of diseases that are caused by defects in protein trafficking [40][41][42][43] . Although these new insights provide no prospect for therapy, they open up the option of prenatal diagnosis.…”

Peroxisome Function, Biogenesis, and Dynamics in Plants

“…In humans, alternative splicing produces two PEX5 forms: a short form competent for PTS1 import and a long form facilitating both PTS1 and PTS2 import (Dodt et al, 1995;Braverman et al, 1998). Although only one Arabidopsis PEX5 splice form is reported, rice contains alternative forms, and only the long form binds PEX7 (Lee et al, 2006).…”