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PMID: 10562279 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

PEX12 interacts with PEX5 and PEX10 and acts downstream of receptor docking in peroxisomal matrix protein import.

The Journal of cell biology ·Vol. 147 ·No. 4 ·1999-11-15 ·Pages 761-74

Chang CC, Warren DS, Sacksteder KA, Gould SJ

Abstract

Peroxisomal matrix protein import requires PEX12, an integral peroxisomal membrane protein with a zinc ring domain at its carboxy terminus. Mutations in human PEX12 result in Zellweger syndrome, a lethal neurological disorder, and implicate the zinc ring domain in PEX12 function. Using two-hybrid studies, blot overlay assays, and coimmunoprecipitation experiments, we observed that the zinc-binding domain of PEX12 binds both PEX5, the PTS1 receptor, and PEX10, another integral peroxisomal membrane protein required for peroxisomal matrix protein import. Furthermore, we identified a patient with a missense mutation in the PEX12 zinc-binding domain, S320F, and observed that this mutation reduces the binding of PEX12 to PEX5 and PEX10. Overexpression of either PEX5 or PEX10 can suppress this PEX12 mutation, providing genetic evidence that these interactions are biologically relevant. PEX5 is a predominantly cytoplasmic protein and previous PEX5-binding proteins have been implicated in docking PEX5 to the peroxisome surface. However, we find that loss of PEX12 or PEX10 does not reduce the association of PEX5 with peroxisomes, demonstrating that these peroxins are not required for receptor docking. These and other results lead us to propose that PEX12 and PEX10 play direct roles in peroxisomal matrix protein import downstream of the receptor docking event.

MeSH Terms
Alleles Amino Acid Sequence Base Sequence Cell Line DNA/genetics DNA Primers Humans Membrane Proteins/chemistry,genetics,metabolism Molecular Sequence Data Mutation Open Reading Frames Peroxins Peroxisomal Disorders/genetics,metabolism,pathology Peroxisome-Targeting Signal 1 Receptor Peroxisomes/metabolism Point Mutation Protein Binding Protein Biosynthesis Receptors, Cytoplasmic and Nuclear/metabolism Recombinant Proteins/metabolism Repetitive Sequences, Amino Acid Repetitive Sequences, Nucleic Acid Skin/metabolism,pathology Transfection Zellweger Syndrome/genetics
Chemicals
DNA Primers Membrane Proteins PEX10 protein, human PEX12 protein, human PEX5 protein, human Peroxins Peroxisome-Targeting Signal 1 Receptor Receptors, Cytoplasmic and Nuclear Recombinant Proteins DNA
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Chang C C
The Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Warren D S
Sacksteder K A
Gould S J
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.147.4.761
Published
1999-11-15
Pages
761-74
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2156163
Subset
IM
Grants
NIDDK NIH HHS · DK45787 · United States
NICHD NIH HHS · HD10987 · United States
External Links
PubMed source DOI: 10.1083/jcb.147.4.761 PMC Full Text View journal details
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