title: The 22-kD peroxisomal integral membrane protein in Zellweger syndrome--presence, abundance, and association with a peroxisomal thiolase precursor protein.
abstract: The primary genetic defect of Zellweger syndrome may be related to defective synthesis or impaired import of peroxisomal proteins. We analyzed the presence and measured the abundance of the 22-kD peroxisomal integral membrane protein (PMP) in patients with Zellweger syndrome. We determined the intracellular localization of the 22-kD PMP and compared it with the localization of a peroxisomal 44-kD thiolase precursor protein. The 22-kD PMP was quantified by immunoblot analyses in liver tissue (n = 7 patients). Immunoblot signals were evaluated using transmission photometry. The intracellular localization of the 22-kD PMP and the peroxisomal 44-kD thiolase precursor protein were determined by immunoblot analyses on fibroblast subcellular fractions prepared by Nycodenz (n = 5 patients) or sucrose density gradient centrifugation (n = 2 patients). The 22-kD PMP was present and associated with membrane fractions in all patients. Its abundance varied in patients as compared with normal human liver controls. The 22-kD PMP was located in subcellular membrane fractions having a lower density than normal peroxisomes or mitochondria. Using two different gradient techniques, the 22-kD PMP and the peroxisomal 44-kD thiolase precursor protein were found in the same low-density gradient fractions. These results suggest that in Zellweger syndrome peroxisome-like elements containing both the 22-kD PMP and a 44-kD thiolase precursor protein are formed. Globally defective synthesis or import of peroxisomal proteins is therefore unlikely to be the primary genetic defect in the patients we studied.
authors.affiliation: Kennedy Institute for Handicapped Children, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205.
authors.forename: J
authors.initials: J
authors.lastname: Gärtner
authors.forename: W W
authors.initials: WW
authors.lastname: Chen
authors.forename: R I
authors.initials: RI
authors.lastname: Kelley
authors.forename: S J
authors.initials: SJ
authors.lastname: Mihalik
authors.forename: H W
authors.initials: HW
authors.lastname: Moser
mesh_terms: D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D008830:Microbodies / Q000378:metabolism*; D008970:Molecular Weight; D011498:Protein Precursors / Q000378:metabolism; D013347:Subcellular Fractions / Q000378:metabolism; D015211:Zellweger Syndrome / Q000378:metabolism* / Q000473:pathology
chemical_list: D008565:Membrane Proteins; D011498:Protein Precursors; D000101:Acetyl-CoA C-Acetyltransferase