title: Assembly of Peroxisomal Membrane Proteins via the Direct Pex19p-Pex3p Pathway.
abstract: Correct targeting of peroxisomal membrane proteins (PMPs) is essential for the formation and maintenance of functional peroxisomes. Activities of Pex19p to interact with PMPs on one hand and Pex3p on the other, including formation of ternary complexes between Pex19p, PMP and Pex3p, strongly support posttranslational translocation of PMPs via the Pex19p- and Pex3p-dependent direct pathway, termed the class I pathway. However, it remains elusive whether Pex19p-PMP complexes are indeed capable of being imported into peroxisomal membranes through the interaction between Pex19p and Pex3p. We resolve this issue by investigating the targeting process of several topologically distinct PMPs, including multimembrane spanning PMPs. We show here that Pex19p forms cytosolic complexes with PMPs and directly translocates them to peroxisomes. Using a semi-intact mammalian cell-based import assay system, we prove that PMPs in the cytosolic complexes are imported into peroxisomes via the interaction between cargo-loaded Pex19p and Pex3p. Furthermore, we demonstrate for the first time that peroxisomal targeting of ATAD1, an N-terminally signal-anchored protein that resides on both mitochondria and peroxisomes, is also achieved through the Pex19p- and Pex3p-dependent class I pathway. Together, our results suggest that translocation of PMPs via the class I pathway is a common event in mammalian cells.
authors.affiliation: Graduate School of Systems Life Sciences, Kyushu University Graduate School, Nishi-ku, Fukuoka, 819-0395, Japan.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biology, Faculty of Sciences, Kyushu University, Nishi-ku, Fukuoka, 819-0395, Japan.|Present address: Department of Infectious Disease Control, International Research Center for Infectious Diseases, The Institute of Medical Science, The University of Tokyo, Tokyo, 108-8639, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Yagita
authors.affiliation: Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, 812-8582, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Fujiki
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006367:HeLa Cells; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D000074401:Peroxins; D020675:Peroxisomes / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D008074:Lipoproteins; D008565:Membrane Proteins; D000074401:Peroxins; C113138:Pex3 protein, human; C087343:PEX19 protein, human
keywords: Pex19p; Pex3p; class I pathway; direct import; membrane assembly; peroxisomal membrane protein; peroxisome; protein trafficking