title: PEX19 is a predominantly cytosolic chaperone and import receptor for class 1 peroxisomal membrane proteins.
abstract: Integral peroxisomal membrane proteins (PMPs) are synthesized in the cytoplasm and imported posttranslationally. Here, we demonstrate that PEX19 binds and stabilizes newly synthesized PMPs in the cytosol, binds to multiple PMP targeting signals (mPTSs), interacts with the hydrophobic domains of PMP targeting signals, and is essential for PMP targeting and import. These results show that PEX19 functions as both a chaperone and an import receptor for newly synthesized PMPs. We also demonstrate the existence of two PMP import mechanisms and two classes of mPTSs: class 1 mPTSs, which are bound by PEX19 and imported in a PEX19-dependent manner, and class 2 mPTSs, which are not bound by PEX19 and mediate protein import independently of PEX19.
authors.affiliation: Dept. of Biological Chemistry, The Johns Hopkins University School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Jacob M
authors.initials: JM
authors.lastname: Jones
authors.forename: James C
authors.initials: JC
authors.lastname: Morrell
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Gould
mesh_terms: D002460:Cell Line; D003600:Cytosol / Q000378:metabolism* / Q000648:ultrastructure; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism* / Q000648:ultrastructure; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000378:metabolism; D018832:Molecular Chaperones / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism* / Q000648:ultrastructure; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D015398:Signal Transduction / Q000502:physiology
chemical_list: D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018832:Molecular Chaperones; C087343:PEX19 protein, human