title: Saccharomyces cerevisiae pex3p and pex19p are required for proper localization and stability of peroxisomal membrane proteins.
abstract: The mechanisms by which peroxisomal membrane proteins (PMPs) are targeted to and inserted into membranes are unknown, as are the required components. We show that among a collection of 16 Saccharomyces cerevisiae peroxisome biogenesis (pex) mutants, two mutants, pex3Delta and pex19Delta, completely lack detectable peroxisomal membrane structures and mislocalize their PMPs to the cytosol where they are rapidly degraded. The other pexDelta mutants contain membrane structures that are properly inherited during vegetative growth and that house multiple PMPs. Even Pex15p requires Pex3p and Pex19p for localization to peroxisomal membranes. This PMP was previously hypothesized to travel via the endoplasmic reticulum (ER) to peroxisomes. We provide evidence that ER-accumulated Pex15p is not a sorting intermediate on its way to peroxisomes. Our results show that Pex3p and Pex19p are required for the proper localization of all PMPs tested, including Pex15p, whereas the other Pex proteins might only be required for targeting/import of matrix proteins.
authors.affiliation: Department of Biochemistry, University of Amsterdam, Academic Medical Center, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.
authors.forename: E H
authors.initials: EH
authors.lastname: Hettema
authors.forename: W
authors.initials: W
authors.lastname: Girzalsky
authors.forename: M
authors.initials: M
authors.lastname: van Den Berg
authors.forename: R
authors.initials: R
authors.lastname: Erdmann
authors.forename: B
authors.initials: B
authors.lastname: Distel
mesh_terms: D018528:ATP-Binding Cassette Transporters; D003600:Cytosol / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D017353:Gene Deletion; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008854:Microscopy, Electron; D016296:Mutagenesis; D000074401:Peroxins; D020675:Peroxisomes / Q000502:physiology* / Q000648:ultrastructure; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins
chemical_list: D018528:ATP-Binding Cassette Transporters; D005656:Fungal Proteins; D008565:Membrane Proteins; C109779:PEX19 protein, S cerevisiae; C070895:PEX3 protein, S cerevisiae; D000074401:Peroxins; C406793:SPF1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins