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Title: Direct visualization of degradation microcompartments at the ER membrane

Abstract

To promote the biochemical reactions of life, cells can compartmentalize molecular interaction partners together within separated non–membrane-bound regions. It is unknown whether this strategy is used to facilitate protein degradation at specific locations within the cell. Leveraging in situ cryo-electron tomography to image the native molecular landscape of the unicellular alga Chlamydomonas reinhardtii , we discovered that the cytosolic protein degradation machinery is concentrated within ∼200-nm foci that contact specialized patches of endoplasmic reticulum (ER) membrane away from the ER–Golgi interface. These non–membrane-bound microcompartments exclude ribosomes and consist of a core of densely clustered 26S proteasomes surrounded by a loose cloud of Cdc48. Active proteasomes in the microcompartments directly engage with putative substrate at the ER membrane, a function canonically assigned to Cdc48. Live-cell fluorescence microscopy revealed that the proteasome clusters are dynamic, with frequent assembly and fusion events. We propose that the microcompartments perform ER-associated degradation, colocalizing the degradation machinery at specific ER hot spots to enable efficient protein quality control.

Authors:
; ; ; ; ; ; ORCiD logo; ORCiD logo; ; ORCiD logo
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1580556
Grant/Contract Number:  
FC02-02ER63421
Resource Type:
Published Article
Journal Name:
Proceedings of the National Academy of Sciences of the United States of America
Additional Journal Information:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Volume: 117 Journal Issue: 2; Journal ID: ISSN 0027-8424
Publisher:
Proceedings of the National Academy of Sciences
Country of Publication:
United States
Language:
English

Citation Formats

Albert, Sahradha, Wietrzynski, Wojciech, Lee, Chia-Wei, Schaffer, Miroslava, Beck, Florian, Schuller, Jan M., Salomé, Patrice A., Plitzko, Jürgen M., Baumeister, Wolfgang, and Engel, Benjamin D. Direct visualization of degradation microcompartments at the ER membrane. United States: N. p., 2019. Web. doi:10.1073/pnas.1905641117.
Albert, Sahradha, Wietrzynski, Wojciech, Lee, Chia-Wei, Schaffer, Miroslava, Beck, Florian, Schuller, Jan M., Salomé, Patrice A., Plitzko, Jürgen M., Baumeister, Wolfgang, & Engel, Benjamin D. Direct visualization of degradation microcompartments at the ER membrane. United States. doi:10.1073/pnas.1905641117.
Albert, Sahradha, Wietrzynski, Wojciech, Lee, Chia-Wei, Schaffer, Miroslava, Beck, Florian, Schuller, Jan M., Salomé, Patrice A., Plitzko, Jürgen M., Baumeister, Wolfgang, and Engel, Benjamin D. Fri . "Direct visualization of degradation microcompartments at the ER membrane". United States. doi:10.1073/pnas.1905641117.
@article{osti_1580556,
title = {Direct visualization of degradation microcompartments at the ER membrane},
author = {Albert, Sahradha and Wietrzynski, Wojciech and Lee, Chia-Wei and Schaffer, Miroslava and Beck, Florian and Schuller, Jan M. and Salomé, Patrice A. and Plitzko, Jürgen M. and Baumeister, Wolfgang and Engel, Benjamin D.},
abstractNote = {To promote the biochemical reactions of life, cells can compartmentalize molecular interaction partners together within separated non–membrane-bound regions. It is unknown whether this strategy is used to facilitate protein degradation at specific locations within the cell. Leveraging in situ cryo-electron tomography to image the native molecular landscape of the unicellular alga Chlamydomonas reinhardtii , we discovered that the cytosolic protein degradation machinery is concentrated within ∼200-nm foci that contact specialized patches of endoplasmic reticulum (ER) membrane away from the ER–Golgi interface. These non–membrane-bound microcompartments exclude ribosomes and consist of a core of densely clustered 26S proteasomes surrounded by a loose cloud of Cdc48. Active proteasomes in the microcompartments directly engage with putative substrate at the ER membrane, a function canonically assigned to Cdc48. Live-cell fluorescence microscopy revealed that the proteasome clusters are dynamic, with frequent assembly and fusion events. We propose that the microcompartments perform ER-associated degradation, colocalizing the degradation machinery at specific ER hot spots to enable efficient protein quality control.},
doi = {10.1073/pnas.1905641117},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 2,
volume = 117,
place = {United States},
year = {2019},
month = {12}
}

Journal Article:
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DOI: 10.1073/pnas.1905641117

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