SGTA regulates the cytosolic quality control of hydrophobic substrates

Lydia Wunderley, Pawel Leznicki, Aishwarya Payapilly, Stephen High (Lead / Corresponding author)

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    Abstract

    Hydrophobic amino acids are normally shielded from the cytosol and their exposure is often used as an indicator of protein misfolding to enable the chaperone-mediated recognition and quality control of aberrant polypeptides. Mislocalised membrane proteins (MLPs) represent a particular challenge to cellular quality control, and, in this study, membrane protein fragments have been exploited to study a specialised pathway that underlies the efficient detection and proteasomal degradation of MLPs. Our data show that the BAG6 complex and SGTA compete for cytosolic MLPs by recognition of their exposed hydrophobicity, and the data suggest that SGTA acts to maintain these substrates in a non-ubiquitylated state. Hence, SGTA might counter the actions of BAG6 to delay the ubiquitylation of specific precursors and thereby increase their opportunity for successful post-translational delivery to the endoplasmic reticulum. However, when SGTA is overexpressed, the normally efficient removal of aberrant MLPs is delayed, increasing their steady-state level and promoting aggregation. Our data suggest that SGTA regulates the cellular fate of a range of hydrophobic polypeptides should they become exposed to the cytosol.

    Original languageEnglish
    Pages (from-to)4728-4739
    Number of pages12
    JournalJournal of Cell Science
    Volume127
    Issue number21
    DOIs
    Publication statusPublished - 1 Nov 2014

    Keywords

    • Aggresomes
    • BAG6
    • Mislocalised membrane proteins
    • Polyubiquitylation
    • Protein degradation
    • Small glutaminerich tetratricopeptide repeat-containing protein alpha

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  • Cite this

    Wunderley, L., Leznicki, P., Payapilly, A., & High, S. (2014). SGTA regulates the cytosolic quality control of hydrophobic substrates. Journal of Cell Science, 127(21), 4728-4739. https://doi.org/10.1242/jcs.155648