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ORIGINAL RESEARCH article

Front. Mol. Biosci.
Sec. Protein Biochemistry for Basic and Applied Sciences
Volume 11 - 2024 | doi: 10.3389/fmolb.2024.1427542
This article is part of the Research Topic Celebrating Women’s Contribution to Protein Folding, Misfolding, and Degradation In Honor of Susan Lindquist (1949-2016) View all 8 articles

Clearing the JUNQ: the molecular machinery for sequestration, localization, and degradation of the JUNQ compartment

Provisionally accepted
Sarah Rolli Sarah Rolli Chloe A. Langridge Chloe A. Langridge Emily M. Sontag Emily M. Sontag *
  • Marquette University, Milwaukee, United States

The final, formatted version of the article will be published soon.

    Cellular protein homeostasis (proteostasis) plays an essential role in regulating the folding, sequestration, and turnover of misfolded proteins via a network of chaperones and clearance factors. Previous work has shown that misfolded proteins are spatially sequestered into membrane-less compartments in the cell as part of the proteostasis process. Soluble misfolded proteins in the cytoplasm are trafficked into the juxtanuclear quality control compartment (JUNQ), and nuclear proteins are sequestered into the intranuclear quality control compartment (INQ). However, the mechanisms that control the formation, localization, and degradation of these compartments are unknown. Previously, we showed that the JUNQ migrates to the nuclear membrane adjacent to the INQ at nucleus-vacuole junctions (NVJ), and the INQ moves through the NVJ into the vacuole for clearance in an ESCRTmediated process. Here we have investigated what mechanisms are involved in the formation, migration, and clearance of the JUNQ. We find Hsp70s Ssa1 and Ssa2 are required for JUNQ localization to the NVJ and degradation of cytoplasmic misfolded proteins. We also confirm that sequestrases Btn2 and Hsp42 sort misfolded proteins to the JUNQ or IPOD, respectively. Interestingly, proteins required for piecemeal microautophagy of the nucleus (PMN) (i.e. Nvj1, Vac8, Atg1, and Atg8) drive the formation and clearance of the JUNQ. This suggests that the JUNQ migrates to the NVJ to be cleared via microautophagy.

    Keywords: protein misfolding, proteostasis, Microautophagy, Piecemeal microautophagy of the nucleus, spatial sequestration

    Received: 03 May 2024; Accepted: 25 Jul 2024.

    Copyright: © 2024 Rolli, Langridge and Sontag. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Emily M. Sontag, Marquette University, Milwaukee, United States

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