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 biogenesi s. Targeting by this pathway is known to involve the interaction of oligope ptide PTS2 signals with Pex7p, the PTS2 receptor. Pex7p function is conserv ed between yeasts and humans, with defects in the human protein causing rhi zomelic chondrodysplasia punctata (RCDP), a severe, lethal peroxisome bioge nesis disorder characterized by aberrant targeting of several PTS2 peroxiso mal proteins, but uncertainty remains about the subcellular localization of this receptor. Previously, we have reported that ScPex7p resides predomina ntly in the peroxisomal matrix, suggesting that it may function as a highly unusual intraorganellar import receptor, and the data presented in this pa per identify Pex18p and Pex21p as key components in the targeting of Pex7p to peroxisomes. They each interact specifically with Pex7p both in two-hybr id analyses and in vitro. In cells lacking both Pex18p and Pex21p, Pex7p re mains cytosolic and PTS2 targeting is completely abolished. Pex18p and Pex2 1p are weakly homologous to each other and display partial functional redun dancy, indicating that they constitute a two-member peroxin family specific ally required for Pex7p and PTS2 targeting.