Cell Biology

The cellular architecture of ERAD

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Science  31 Jan 2020:
Vol. 367, Issue 6477, pp. 523-524
DOI: 10.1126/science.367.6477.523-d

Endoplasmic reticulum (ER)–associated degradation (ERAD) is an evolutionarily conserved quality control mechanism whereby misfolded proteins are removed from the ER and degraded in the cytosol by the ubiquitin-proteasome system. Many ERAD-mediating proteins have been identified, but their spatial organization within the cell is less well established. Albert et al. used in situ cryo–electron tomography to image the native molecular landscape within Chlamydomonas cells. They found that ERAD proteins concentrated within ∼200-nanometer cytosolic foci that contacted the ER membrane away from the ER-Golgi interface. The ribosome-excluding ERAD microcompartments consisted of a core of clustered proteasomes surrounded by Cdc48. Within these clusters, active proteasomes appeared to engage directly with substrates at the ER membrane, a function thought to be performed by Cdc48. In live-cell imaging experiments, the proteasome clusters were seen to form dynamically, possibly by liquid-liquid phase separation. This dynamic, but well-defined, architecture of ERAD machinery likely contributes to efficient protein quality control.

Proc. Natl. Acad. Sci. U.S.A. 117, 1069 (2020).

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