title: Distinct requirements for intra-ER sorting and budding of peroxisomal membrane proteins from the ER.
abstract: During de novo peroxisome biogenesis, importomer complex proteins sort via two preperoxisomal vesicles (ppVs). However, the sorting mechanisms segregating peroxisomal membrane proteins to the preperoxisomal endoplasmic reticulum (pER) and into ppVs are unknown. We report novel roles for Pex3 and Pex19 in intra-endoplasmic reticulum (ER) sorting and budding of the RING-domain peroxins (Pex2, Pex10, and Pex12). Pex19 bridged the interaction at the ER between Pex3 and RING-domain proteins, resulting in a ternary complex that was critical for the intra-ER sorting and subsequent budding of the RING-domain peroxins. Although the docking subcomplex proteins (Pex13, Pex14, and Pex17) also required Pex19 for budding from the ER, they sorted to the pER independently of Pex3 and Pex19 and were spatially segregated from the RING-domain proteins. We also discovered a unique role for Pex3 in sorting Pex10 and Pex12, but with the docking subcomplex. Our study describes an intra-ER sorting process that regulates segregation, packaging, and budding of peroxisomal importomer subcomplexes, thereby preventing their premature assembly at the ER.
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Agrawal
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Scott N
authors.initials: SN
authors.lastname: Fassas
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093.
authors.forename: Zhi-Jie
authors.initials: ZJ
authors.lastname: Xia
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093 ssubramani@ucsd.edu.
authors.forename: Suresh
authors.initials: S
authors.lastname: Subramani
mesh_terms: D004721:Endoplasmic Reticulum / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D046912:Multiprotein Complexes; D020675:Peroxisomes / Q000378:metabolism*; D010843:Pichia / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D021381:Protein Transport; D013997:Time Factors
chemical_list: D005656:Fungal Proteins; D008565:Membrane Proteins; D046912:Multiprotein Complexes
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