title: Molecular mechanism of detectable catalase-containing particles, peroxisomes, in fibroblasts from a PEX2-defective patient.
abstract: Patients with peroxisome biogenesis disorders (PBD) can be identified by detection of peroxisomes in their fibroblasts, by means of immunocytochemical staining using an anti-catalase antibody. We report here data on three PBD patients with newly identified mutations (del550C and del642G) in the PEX2 gene which encodes a 35-kDa peroxisomal membrane protein containing two membrane-spanning and a C-terminal cysteine-rich region. Some of the fibroblasts from the patient with the del642G mutation contained numerous catalase-containing particles, whereas no fibroblasts containing such particles were found in the patient with the del550C mutation. We confirmed that the del642G mutation caused a partial defect in peroxisome synthesis and import by expression of the mutated PEX2 into PEX2-defective CHO mutant cells. We propose that the two putative membrane-spanning segments in Pex2p are important domains for peroxisome assembly and import and that a defect in one of these domains severely affects PBD patients. Furthermore, a defect in the C-terminal portion of Pex2p exposed to the cytosol containing a RING finger motif caused the mild phenotype, residual enzyme activities, and mosaic detectable peroxisomes in fibroblasts from the patient.
authors.affiliation: Department of Pediatrics, Gifu University School of Medicine, Gifu, 500-8076, Japan. nshim@cc.gifu-u.ac.jp
authors.forename: N
authors.initials: N
authors.lastname: Shimozawa
authors.forename: Z
authors.initials: Z
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: Imamura
authors.forename: Y
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Y
authors.initials: Y
authors.lastname: Fujiki
authors.forename: T
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: T
authors.initials: T
authors.lastname: Osumi
authors.forename: P
authors.initials: P
authors.lastname: Aubourg
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: N
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002374:Catalase / Q000378:metabolism*; D002460:Cell Line; D002675:Child, Preschool; D006224:Cricetinae; D004247:DNA / Q000235:genetics; D005260:Female; D005347:Fibroblasts / Q000201:enzymology / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D000074428:Peroxisomal Biogenesis Factor 2; D018901:Peroxisomal Disorders / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D020675:Peroxisomes / Q000201:enzymology*; D017384:Sequence Deletion
chemical_list: D008565:Membrane Proteins; C000614230:PEX2 protein, human; D000074428:Peroxisomal Biogenesis Factor 2; D004247:DNA; D002374:Catalase