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.
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15 November 1999
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November 15 1999
Pex12 Interacts with Pex5 and Pex10 and Acts Downstream of Receptor Docking in Peroxisomal Matrix Protein Import
Chia-Che Chang,
Chia-Che Chang
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Daniel S. Warren,
Daniel S. Warren
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Katherine A. Sacksteder,
Katherine A. Sacksteder
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Stephen J. Gould
Stephen J. Gould
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
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Chia-Che Chang
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Daniel S. Warren
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Katherine A. Sacksteder
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
Stephen J. Gould
aThe Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205
1.used in this paper: MBP, maltose-binding protein; ORF, open reading frame; PBD, peroxisome biogenesis disorder; PMP, peroxisomal membrane protein
Received:
August 23 1999
Revision Requested:
October 08 1999
Accepted:
October 12 1999
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Cell Biol (1999) 147 (4): 761–774.
Article history
Received:
August 23 1999
Revision Requested:
October 08 1999
Accepted:
October 12 1999
Citation
Chia-Che Chang, Daniel S. Warren, Katherine A. Sacksteder, Stephen J. Gould; Pex12 Interacts with Pex5 and Pex10 and Acts Downstream of Receptor Docking in Peroxisomal Matrix Protein Import. J Cell Biol 15 November 1999; 147 (4): 761–774. doi: https://doi.org/10.1083/jcb.147.4.761
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