Direct visualization of degradation microcompartments at the ER membrane

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.. (2020) Direct visualization of degradation microcompartments at the ER membrane. Proceedings of the National Academy of Sciences of the United States of America, 117 (2). pp. 1069-1080.

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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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Structural Biology & Biophysics > Structural Biology and Biophysics (Engel)
UniBasel Contributors:Engel, Ben and Wietrzynski, Wojciech
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:National Academy of Sciences
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:23 Aug 2022 10:38
Deposited On:23 Aug 2022 10:38

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