title: Tail-anchored PEX26 targets peroxisomes via a PEX19-dependent and TRC40-independent class I pathway.
abstract: Tail-anchored (TA) proteins are anchored into cellular membranes by a single transmembrane domain (TMD) close to the C terminus. Although the targeting of TA proteins to peroxisomes is dependent on PEX19, the mechanistic details of PEX19-dependent targeting and the signal that directs TA proteins to peroxisomes have remained elusive, particularly in mammals. The present study shows that PEX19 formed a complex with the peroxisomal TA protein PEX26 in the cytosol and translocated it directly to peroxisomes by interacting with the peroxisomal membrane protein PEX3. Unlike in yeast, the adenosine triphosphatase TRC40, which delivers TA proteins to the endoplasmic reticulum, was dispensable for the peroxisomal targeting of PEX26. Moreover, the basic amino acids within the luminal domain of PEX26 were essential for binding to PEX19 and thereby for peroxisomal targeting. Finally, our results suggest that a TMD that escapes capture by TRC40 and is followed by a highly basic luminal domain directs TA proteins to peroxisomes via the PEX19-dependent route.
authors: Graduate School of Systems Life Sciences, Faculty of Sciences, Kyushu University, Higashi-ku, Fukuoka, Japan.
authors: Yuichi
authors: Y
authors: Yagita
authors: Takahide
authors: T
authors: Hiromasa
authors: Yukio
authors: Y
authors: Fujiki
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D053501:Arsenite Transporting ATPases / Q000235:genetics / Q000378:metabolism*; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D003600:Cytosol / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D000074401:Peroxins; D020675:Peroxisomes / Q000378:metabolism*; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs; D025941:Protein Interaction Mapping; D021382:Protein Sorting Signals; D021381:Protein Transport; D034622:RNA Interference; D000069816:SEC Translocation Channels; D017422:Sequence Analysis, DNA; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D050988:Vesicle-Associated Membrane Protein 2 / Q000378:metabolism
chemical_list: C489667:GET3 protein, human; D008074:Lipoproteins; D008565:Membrane Proteins; C474612:PEX26 protein, human; D000074401:Peroxins; C113138:Pex3 protein, human; D021382:Protein Sorting Signals; D000069816:SEC Translocation Channels; C499388:SEC61B protein, human; C494807:VAMP2 protein, human; D050988:Vesicle-Associated Membrane Protein 2; C087343:PEX19 protein, human; D000255:Adenosine Triphosphate; D053501:Arsenite Transporting ATPases