Abstract
Peroxisomes are components of virtually all eukaryotic cells. While much is known about peroxisomal matrix protein import, our understanding of how peroxisomal membrane proteins (PMPs) are targeted and inserted into the peroxisome membrane is extremely limited. Here, we show that PEX19 binds a broad spectrum of PMPs, displays saturable PMP binding, and interacts with regions of PMPs required for their targeting to peroxisomes. Furthermore, mislocalization of PEX19 to the nucleus leads to nuclear accumulation of newly synthesized PMPs. At steady state, PEX19 is bimodally distributed between the cytoplasm and peroxisome, with most of the protein in the cytoplasm. We propose that PEX19 may bind newly synthesized PMPs and facilitate their insertion into the peroxisome membrane. This hypothesis is supported by the observation that the loss of PEX19 results in degradation of PMPs and/or mislocalization of PMPs to the mitochondrion.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Biological Transport / physiology
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Cell Nucleus / metabolism
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Cytoplasm / metabolism*
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Fibroblasts / cytology
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Fibroblasts / metabolism
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Fluorescent Antibody Technique
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Fungal Proteins / genetics
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Fungal Proteins / metabolism
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Genetic Vectors
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Humans
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Intracellular Membranes / metabolism*
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mitochondria / metabolism
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Molecular Chaperones*
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Nuclear Localization Signals / genetics
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Peptide Fragments / genetics
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Peptide Fragments / metabolism
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Peroxisomes / metabolism*
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Protein Binding / physiology
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Rats
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Recombinant Proteins / genetics
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Recombinant Proteins / metabolism
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Repressor Proteins*
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Transfection
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Two-Hybrid System Techniques
Substances
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Fungal Proteins
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Membrane Proteins
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Molecular Chaperones
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Nuclear Localization Signals
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PEX14 protein, human
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PEX19 protein, rat
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Peptide Fragments
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Pex14 protein, rat
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Recombinant Proteins
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Repressor Proteins