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Titel: Quantitative Proteomics and Differential Protein Abundance Analysis after the Depletion of PEX3 from Human Cells Identifies Additional Aspects of Protein Targeting to the ER
VerfasserIn: Zimmermann, Richard
Lang, Sven
Lerner, Monika
Förster, Friedrich
Nguyen, Duy
Helms, Volkhard
Schrul, Bianca
Sprache: Englisch
Titel: International Journal of Molecular Sciences
Bandnummer: 22
Heft: 23
Verlag/Plattform: MDPI
Erscheinungsjahr: 2021
Freie Schlagwörter: endoplasmic reticulum
lipid droplets
peroxisomes
PEX3
protein targeting
membrane protein insertion
protein translocation
label-free quantitative mass spectrometry
differential protein abundance analysis
Zellweger syndrome
DDC-Sachgruppe: 500 Naturwissenschaften
610 Medizin, Gesundheit
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Protein import into the endoplasmic reticulum (ER) is the first step in the biogenesis of around 10,000 different soluble and membrane proteins in humans. It involves the co- or post translational targeting of precursor polypeptides to the ER, and their subsequent membrane insertion or translocation. So far, three pathways for the ER targeting of precursor polypeptides and four pathways for the ER targeting of mRNAs have been described. Typically, these pathways deliver their substrates to the Sec61 polypeptide-conducting channel in the ER membrane. Next, the pre cursor polypeptides are inserted into the ER membrane or translocated into the ER lumen, which may involve auxiliary translocation components, such as the TRAP and Sec62/Sec63 complexes, or auxiliary membrane protein insertases, such as EMC and the TMCO1 complex. Recently, the PEX19/PEX3-dependent pathway, which has a well-known function in targeting and inserting vari ous peroxisomal membrane proteins into pre-existent peroxisomal membranes, was also found to act in the targeting and, putatively, insertion of monotopic hairpin proteins into the ER. These either remain in the ER as resident ER membrane proteins, or are pinched off from the ER as components of new lipid droplets. Therefore, the question arose as to whether this pathway may play a more general role in ER protein targeting, i.e., whether it represents a fourth pathway for the ER targeting of precursor polypeptides. Thus, we addressed the client spectrum of the PEX19/PEX3-dependent pathway in both PEX3-depleted HeLa cells and PEX3-deficient Zellweger patient fibroblasts by an established approach which involved the label-free quantitative mass spectrometry of the total proteome of depleted or deficient cells, as well as differential protein abundance analysis. The negatively affected proteins included twelve peroxisomal proteins and two hairpin proteins of the ER, thus confirming two previously identified classes of putative PEX19/PEX3 clients in human cells. Interestingly, fourteen collagen-related proteins with signal peptides or N-terminal transmembrane helices belonging to the secretory pathway were also negatively affected by PEX3 deficiency, which may suggest compromised collagen biogenesis as a hitherto-unknown contributor to organ failures in the respective Zellweger patients.
DOI der Erstveröffentlichung: 10.3390/ijms222313028
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-351074
hdl:20.500.11880/32140
http://dx.doi.org/10.22028/D291-35107
ISSN: 1422-0067
Datum des Eintrags: 6-Jan-2022
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Material
In Beziehung stehendes Objekt: https://www.mdpi.com/1422-0067/22/23/13028/s1
Fakultät: M - Medizinische Fakultät
NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: M - Medizinische Biochemie und Molekularbiologie
NT - Biowissenschaften
Professur: M - Keiner Professur zugeordnet
NT - Prof. Dr. Volkhard Helms
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes

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