Chapter 296 - Protein Quality Control in Peroxisomes: Ubiquitination of the Peroxisomal Targeting Signal Receptors

Abstract

This chapter discusses the ubiquitination of the PTS (co-) receptors and addresses the role of each of the proteins involved in this process together with the implications of receptor ubiquitination on peroxisomal matrix protein import. Proteins destined for the peroxisomal matrix begin their journey in the cytosol, where they are synthesized on free polyribosomes. Peroxisomal sorting, like the sorting into other subcellular compartments, relies on targeting signals, in this case a peroxisomal targeting signal (PTS). Ubiquitination is the attachment of ubiquitin to a substrate protein. Either mono- or poly-ubiquitination of Pex5p is required to remove the protein from the peroxisomal membrane. In the absence of one of these pathways, the other is capable of taking over. After completion of the docking and PTS translocation steps, the membrane associated PTS (co-) receptor is mono-ubiquitinated by Pex4p, allowing recognition by the AAA proteins, Pex1p and Pex6p. The PTS (co-) receptor is then pulled out of the membrane and the ubiquitin is removed by the de-ubiquitinating enzyme. The PTS (co-) receptor is then free to partake in another round of PTS protein import. In the situation that no efficient recycling is possible, due to the absence of one of the peroxins involved in recycling or in certain PTS (co-) receptor mutants, PTS (co-) receptor poly-ubiquitination, mediated by Ubc4p, is observed. This modified form is then removed from the membrane and destroyed by the 26S proteasome, effectively removing the blockage.