Pex18p and Pex21p, a novel pair of related peroxins essential for peroxisomal targeting by the PTS2 pathway.
We have identified ScPex18p and ScPex21p, two novel S. cerevisiae peroxins required for protein targeting via the PTS2 branch of peroxisomal biogenesis. Targeting by this pathway is known to involve the interaction of oligopeptide PTS2 signals with Pex7p, the PTS2 receptor. Pex7p function is conserved between yeasts and humans, with defects in the human protein causing rhizomelic chondrodysplasia punctata (RCDP), a severe, lethal peroxisome biogenesis disorder characterized by aberrant targeting of several PTS2 peroxisomal proteins, but uncertainty remains about the subcellular localization of this receptor. Previously, we have reported that ScPex7p resides predominantly in the peroxisomal matrix, suggesting that it may function as a highly unusual intraorganellar import receptor, and the data presented in this paper identify Pex18p and Pex21p as key components in the targeting of Pex7p to peroxisomes. They each interact specifically with Pex7p both in two-hybrid analyses and in vitro. In cells lacking both Pex18p and Pex21p, Pex7p remains cytosolic and PTS2 targeting is completely abolished. Pex18p and Pex21p are weakly homologous to each other and display partial functional redundancy, indicating that they constitute a two-member peroxin family specifically required for Pex7p and PTS2 targeting.
Purdue
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Department of Cell Biology and Anatomy, Mount Sinai School of Medicine, New York, New York 10029-6574, USA.epurdue@smtplink.mssm.edu
Yang
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Lazarow
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D000101:Acetyl-CoA C-Acetyltransferase / Q000378:metabolism; D042962:Acyl-CoA Oxidase; D000595:Amino Acid Sequence; D001692:Biological Transport; D002352:Carrier Proteins; D003593:Cytoplasm / Q000737:chemistry; D005656:Fungal Proteins / Q000502:physiology*; D006801:Humans; D008830:Microbodies / Q000378:metabolism* / Q000648:ultrastructure; D008969:Molecular Sequence Data; D009829:Oleic Acids / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism; D000074437:Peroxisomal Targeting Signal 2 Receptor; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins; D016415:Sequence Alignment
D002352:Carrier Proteins; D005656:Fungal Proteins; D009829:Oleic Acids; C116845:PEX18 protein, S cerevisiae; C116846:PEX21 protein, S cerevisiae; D000074437:Peroxisomal Targeting Signal 2 Receptor; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D029701:Saccharomyces cerevisiae Proteins; D010088:Oxidoreductases; D042962:Acyl-CoA Oxidase; C467991:POX1 protein, S cerevisiae; D000101:Acetyl-CoA C-Acetyltransferase