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PMID: 7790377 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

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

The Journal of cell biology ·Vol. 130 ·No. 1 ·1995-07-00 ·Pages 51-65

Wiemer EA, Nuttley WM, Bertolaet BL, Li X, Francke U, Wheelock MJ, Anné UK, Johnson KR, Subramani S

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 pas8 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.

MeSH Terms
Adrenoleukodystrophy/metabolism Amino Acid Sequence Base Sequence Biological Transport Cell Compartmentation Chromosomes, Human, Pair 12 Cloning, Molecular Cytosol/metabolism DNA Primers/chemistry Fungal Proteins Gene Expression Genetic Complementation Test Humans Intracellular Membranes/metabolism Microbodies/metabolism Molecular Sequence Data Peroxisome-Targeting Signal 1 Receptor RNA, Messenger/genetics Receptors, Cytoplasmic and Nuclear/genetics,metabolism Sequence Alignment Sequence Homology, Amino Acid Tissue Distribution Zellweger Syndrome/metabolism
Chemicals
DNA Primers Fungal Proteins PEX5 protein, Pichia pastoris PEX5 protein, human Peroxisome-Targeting Signal 1 Receptor RNA, Messenger Receptors, Cytoplasmic and Nuclear
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Wiemer E A
Department of Biology, University of California at San Diego, La Jolla 92093-0322, USA.
Nuttley W M
Bertolaet B L
Li X
Francke U
Wheelock M J
Anné U K
Johnson K R
Subramani S
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.130.1.51
Published
1995-07-00
Pages
51-65
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2120514
Subset
IM
Grants
NCI NIH HHS · CA44464 · United States
NIGMS NIH HHS · GM41116 · United States
NHGRI NIH HHS · HG00298 · United States
Databases
GENBANK
Z48054
External Links
PubMed source DOI: 10.1083/jcb.130.1.51 PMC Full Text View journal details
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