Pex19p Binds Pex30p and Pex32p at Regions Required for Their Peroxisomal Localization but Separate from Their Peroxisomal Targeting Signals

Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Journal of Biological Chemistry (Impact Factor: 4.57). 06/2006; 281(21):14805-12. DOI: 10.1074/jbc.M601808200
Source: PubMed


The assembly of proteins in the peroxisomal membrane is a multistep process requiring their recognition in the cytosol, targeting to and insertion into the peroxisomal membrane, and stabilization within the lipid bilayer. The peroxin Pex19p has been proposed to be either the receptor that recognizes and targets newly synthesized peroxisomal membrane proteins (PMP) to the peroxisome or a chaperone required for stabilization of PMPs at the peroxisomal membrane. Differentiating between these two roles for Pex19p could be achieved by determining whether the peroxisomal targeting signal (PTS) and the region of Pex19p binding of a PMP are the same or different. We addressed the role for Pex19p in the assembly of two PMPs, Pex30p and Pex32p, of the yeast Saccharomyces cerevisiae. Pex30p and Pex32p control peroxisome size and number but are dispensable for peroxisome formation. Systematic truncations from the carboxyl terminus, together with in-frame deletions of specific regions, have identified PTSs essential for targeting Pex30p and Pex32p to peroxisomes. Both Pex30p and Pex32p interact with Pex19p in regions that do not overlap with their PTSs. However, Pex19p is required for localizing Pex30p and Pex32p to peroxisomes, because mutations that disrupt the interaction of Pex19p with Pex30p and Pex32p lead to their mislocalization to a compartment other than peroxisomes. Mutants of Pex30p and Pex32p that localize to peroxisomes but produce cells exhibiting the peroxisomal phenotypes of cells lacking these proteins demonstrate that the regions in these proteins that control peroxisomal targeting and cell biological activity are separable. Together, our data show that the interaction of Pex19p with Pex30p and Pex32p is required for their roles in peroxisome biogenesis and are consistent with a chaperone role for Pex19p in stabilizing or maintaining membrane proteins in peroxisomes.

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    • "Peroxisomes are unit membrane-bound organelles, containing peroxidase and catalase activities and contribute to several lipid metabolic pathways and redox homeostasis in eukaryotic cells [6,7]. So far 32 PEX genes have been identified and the encoded peroxins are indispensable for peroxisome biogenesis [8,9]. Peroxisome biogenesis can be induced by the presence of fatty acids, and degradation of the organelle in vacuoles (pexophagy) is in response to glucose [5,10,11]. "
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    PLoS ONE 11/2013; 8(11):e79128. DOI:10.1371/journal.pone.0079128 · 3.23 Impact Factor
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    • "Requirement of members of the chaperone Hsp70/ Hsp40 family for peroxisomal matrix protein import was demonstrated (Walton et al., 1994; Legakis and Terlecky, 2001). Other molecular chaperones involved in peroxisomal protein import include the peroxin Pex19 (Jones et al., 2004; Vizeacoumar et al., 2006) or the ankyrin repeat protein Ankr2A (Shen et al., 2010). "
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    Molecular biology of the cell 06/2011; 22(11):1896-906. DOI:10.1091/mbc.E10-11-0914 · 4.47 Impact Factor
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    ABSTRACT: Doutoramento em Ciências Biomédicas
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