title: The unique degradation pathway of the PTS2 receptor, Pex7, is dependent on the PTS receptor/coreceptor, Pex5 and Pex20.
abstract: Peroxisomal matrix protein import uses two peroxisomal targeting signals (PTSs). Most matrix proteins use the PTS1 pathway and its cargo receptor, Pex5. The PTS2 pathway is dependent on another receptor, Pex7, and its coreceptor, Pex20. We found that during the matrix protein import cycle, the stability and dynamics of Pex7 differ from those of Pex5 and Pex20. In Pichia pastoris, unlike Pex5 and Pex20, Pex7 is constitutively degraded in wild-type cells but is stabilized in pex mutants affecting matrix protein import. Degradation of Pex7 is more prevalent in cells grown in methanol, in which the PTS2 pathway is nonessential, in comparison with oleate, suggesting regulation of Pex7 turnover. Pex7 must shuttle into and out of peroxisomes before it is polyubiquitinated and degraded by the proteasome. The shuttling of Pex7, and consequently its degradation, is dependent on the receptor recycling pathways of Pex5 and Pex20 and relies on an interaction between Pex7 and Pex20. We also found that blocking the export of Pex20 from peroxisomes inhibits PTS1-mediated import, suggesting sharing of limited components in the export of PTS receptors/coreceptors. The shuttling and stability of Pex7 are divergent from those of Pex5 and Pex20, exemplifying a novel interdependence of the PTS1 and PTS2 pathways.
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322.
authors.forename: Danielle
authors.initials: D
authors.lastname: Hagstrom
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322 College of Life Sciences, Shandong Normal University, Jinan, Shandong 250014, China changlema@yahoo.com ssubramani@ucsd.edu.
authors.forename: Changle
authors.initials: C
authors.lastname: Ma
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322.
authors.forename: Soumi
authors.initials: S
authors.lastname: Guha-Polley
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0322 changlema@yahoo.com ssubramani@ucsd.edu.
authors.forename: Suresh
authors.initials: S
authors.lastname: Subramani
mesh_terms: D005656:Fungal Proteins; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D020675:Peroxisomes / Q000502:physiology; D010843:Pichia / Q000378:metabolism*; D021382:Protein Sorting Signals; D055550:Protein Stability; D021381:Protein Transport; D059748:Proteolysis; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D054875:Ubiquitination
chemical_list: D005656:Fungal Proteins; C000614263:PEX5 protein, Pichia pastoris; D000074437:Peroxisomal Targeting Signal 2 Receptor; D000074435:Peroxisome-Targeting Signal 1 Receptor; D021382:Protein Sorting Signals; D018160:Receptors, Cytoplasmic and Nuclear