Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders

Erik A.C. Wiemer, William M. Nuttley, Bonnie L. Bertolaet, Xu Li, Uta Francke, Margaret J. Wheelock, Usha K. Anné, Keith R. Johnson, Suresh Subramani

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Abstract

Two peroxisomal targeting signals, PTS1 and PTS2, are involved in the import of proteins into the peroxisome matrix. Human patients with fatal generalized peroxisomal deficiency disorders fall into at least nine genetic complementation groups. Cells from many of these patients are deficient in the import of PTS1 containing proteins, but the causes of the protein-import defect in these patients are unknown. We have cloned and sequenced the human cDNA homologue (pTS1R) of the Pichia pastoris PAS8 gene, the PTS1 receptor (McCollum, D., E. Monosov, and S. Subramani. 1993. J. Cell Biol. 121:761- 774). The PTS1R mRNA is expressed in all human tissues examined. Antibodies to the human PTS1R recognize this protein in human, monkey, rat, and hamster cells. The protein is localized mainly in the cytosol but is also found to be associated with peroxisomes. Part of the peroxisomal PTS1R protein is tightly bound to the peroxisomal membrane. Antibodies to PTS1R inhibit peroxisomal protein-import of PTS1-containing proteins in a permeabilized CHO cell system. In vitro-translated PTS1R protein specifically binds a serine- lysine-leucine-peptide. A PAS8-PTS1R fusion protein complements the P. pastoris pass mutant. The PTS1R cDNA also complements the PTS1 protein- import defect in skin fibroblasts from patients-belonging to complementation group two-diagnosed as having neonatal adrenoleukodystrophy or Zellweger syndrome. The PTS1R gene has been localized to a chromosomal location where no other peroxisomal disorder genes are known to map. Our findings represent the only case in which the molecular basis of the protein-import deficiency in human peroxisomal disorders is understood.

Original languageEnglish (US)
Pages (from-to)51-65
Number of pages15
JournalJournal of Cell Biology
Volume130
Issue number1
DOIs
StatePublished - Jul 1 1995

Fingerprint

Peroxisomal Disorders
Proteins
Peroxisomes
Complement System Proteins
Complementary DNA
Zellweger Syndrome
Genes
Protein Deficiency
Pichia
CHO Cells
Antibodies
Leucine
Cricetinae
Cytosol
Serine
Lysine
Haplorhini
Fibroblasts
Messenger RNA
Skin

ASJC Scopus subject areas

  • Cell Biology

Cite this

Wiemer, E. A. C., Nuttley, W. M., Bertolaet, B. L., Li, X., Francke, U., Wheelock, M. J., ... Subramani, S. (1995). Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. Journal of Cell Biology, 130(1), 51-65. https://doi.org/10.1083/jcb.130.1.51

Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. / Wiemer, Erik A.C.; Nuttley, William M.; Bertolaet, Bonnie L.; Li, Xu; Francke, Uta; Wheelock, Margaret J.; Anné, Usha K.; Johnson, Keith R.; Subramani, Suresh.

In: Journal of Cell Biology, Vol. 130, No. 1, 01.07.1995, p. 51-65.

Research output: Contribution to journalArticle

Wiemer, Erik A.C. ; Nuttley, William M. ; Bertolaet, Bonnie L. ; Li, Xu ; Francke, Uta ; Wheelock, Margaret J. ; Anné, Usha K. ; Johnson, Keith R. ; Subramani, Suresh. / Human peroxisomal targeting signal-1 receptor restores peroxisomal protein import in cells from patients with fatal peroxisomal disorders. In: Journal of Cell Biology. 1995 ; Vol. 130, No. 1. pp. 51-65.
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