%0 Journal Article %1 fischerPhosphorylationReceptorProtein2023a %A Fischer, Sven %A Bürgi, Jérôme %A Gabay-Maskit, Shiran %A Maier, Renate %A Mastalski, Thomas %A Yifrach, Eden %A Obarska-Kosinska, Agnieszka %A Rudowitz, Markus %A Erdmann, Ralf %A Platta, Harald W. %A Wilmanns, Matthias %A Schuldiner, Maya %A Zalckvar, Einat %A Oeljeklaus, Silke %A Drepper, Friedel %A Warscheid, Bettina %C Germany %D 2023 %J Biological chemistry %K *Peroxisomes/metabolism,*Receptors 1 Cytoplasmic Nuclear/metabolism,Carrier Proteins/metabolism,high-content Receptor/metabolism,Pex5p Signal TPR Transport,Saccharomyces and cerevisiae/metabolism,to_read domain,Phosphorylation,posttranslational localization,Protein modification,protein screen,Humans,mass spectrometry,Peroxisome-Targeting %N 2-3 %P 135--155 %R 10.1515/hsz-2022-0168 %T Phosphorylation of the Receptor Protein Pex5p Modulates Import of Proteins into Peroxisomes. %V 404 %X Peroxisomes are organelles with vital functions in metabolism and their dysfunction is associated with human diseases. To fulfill their multiple roles, peroxisomes import nuclear-encoded matrix proteins, most carrying a peroxisomal targeting signal (PTS) 1. The receptor Pex5p recruits PTS1-proteins for import into peroxisomes; whether and how this process is posttranslationally regulated is unknown. Here, we identify 22 phosphorylation sites of Pex5p. Yeast cells expressing phospho-mimicking Pex5p-S507/523D (Pex5p(2D)) show decreased import of GFP with a PTS1. We show that the binding affinity between a PTS1-protein and Pex5p(2D) is reduced. An in vivo analysis of the effect of the phospho-mimicking mutant on PTS1-proteins revealed that import of most, but not all, cargos is affected. The physiological effect of the phosphomimetic mutations correlates with the binding affinity of the corresponding extended PTS1-sequences. Thus, we report a novel Pex5p phosphorylation-dependent mechanism for regulating PTS1-protein import into peroxisomes. In a broader view, this suggests that posttranslational modifications can function in fine-tuning the peroxisomal protein composition and, thus, cellular metabolism.

@article{fischerPhosphorylationReceptorProtein2023a, abstract = {Peroxisomes are organelles with vital functions in metabolism and their dysfunction is associated with human diseases. To fulfill their multiple roles, peroxisomes import nuclear-encoded matrix proteins, most carrying a peroxisomal targeting signal (PTS) 1. The receptor Pex5p recruits PTS1-proteins for import into peroxisomes; whether and how this process is posttranslationally regulated is unknown. Here, we identify 22 phosphorylation sites of Pex5p. Yeast cells expressing phospho-mimicking Pex5p-S507/523D (Pex5p(2D)) show decreased import of GFP with a PTS1. We show that the binding affinity between a PTS1-protein and Pex5p(2D) is reduced. An in vivo analysis of the effect of the phospho-mimicking mutant on PTS1-proteins revealed that import of most, but not all, cargos is affected. The physiological effect of the phosphomimetic mutations correlates with the binding affinity of the corresponding extended PTS1-sequences. Thus, we report a novel Pex5p phosphorylation-dependent mechanism for regulating PTS1-protein import into peroxisomes. In a broader view, this suggests that posttranslational modifications can function in fine-tuning the peroxisomal protein composition and, thus, cellular metabolism.}, added-at = {2024-05-17T13:01:35.000+0200}, address = {Germany}, author = {Fischer, Sven and B{\"u}rgi, J{\'e}r{\^o}me and {Gabay-Maskit}, Shiran and Maier, Renate and Mastalski, Thomas and Yifrach, Eden and {Obarska-Kosinska}, Agnieszka and Rudowitz, Markus and Erdmann, Ralf and Platta, Harald W. and Wilmanns, Matthias and Schuldiner, Maya and Zalckvar, Einat and Oeljeklaus, Silke and Drepper, Friedel and Warscheid, Bettina}, biburl = {https://www.bibsonomy.org/bibtex/22ea2c68b6aa4fe8caac249d7bed07ff2/warscheidlab}, copyright = {{\copyright} 2022 the author(s), published by De Gruyter, Berlin/Boston.}, doi = {10.1515/hsz-2022-0168}, interhash = {fa8b255a7b34369a6c4ba43e9a3c828e}, intrahash = {2ea2c68b6aa4fe8caac249d7bed07ff2}, issn = {1437-4315 1431-6730}, journal = {Biological chemistry}, keywords = {*Peroxisomes/metabolism,*Receptors 1 Cytoplasmic Nuclear/metabolism,Carrier Proteins/metabolism,high-content Receptor/metabolism,Pex5p Signal TPR Transport,Saccharomyces and cerevisiae/metabolism,to_read domain,Phosphorylation,posttranslational localization,Protein modification,protein screen,Humans,mass spectrometry,Peroxisome-Targeting}, langid = {english}, month = feb, number = {2-3}, pages = {135--155}, pmcid = {PMC9929924}, pmid = {36122347}, timestamp = {2024-05-17T13:01:35.000+0200}, title = {Phosphorylation of the Receptor Protein {{Pex5p}} Modulates Import of Proteins into Peroxisomes.}, volume = 404, year = 2023 }