Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles

Lee, Jason E.; Cathey, Peter I.; Wu, Haobin; Parker, Roy; Voeltz, Gia K.

doi:10.1126/science.aay7108

Cited by 229 publications

(211 citation statements)

References 45 publications

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“…Another interesting possibility is that Vimentin acts as a surface for nucleating Stress Granule formation. Recent reports have demonstrated a similar role for Eisosomes 60 , the Endoplasmic Reticulum 61 , and Late Endosomes 62 . The growing list of membraneless organelle-associated cellular structures opens up the fascinating possibility that different types of cytoplasmic surfaces can prime the ad hoc formation of Stress Granules where needed.…”

Section: Discussionmentioning

confidence: 73%

Vimentin protects differentiating stem cells from stress

Pattabiraman

Azad

Amen

et al. 2020

Sci Rep

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Vimentin is one of the first cytoplasmic intermediate filaments to be expressed in mammalian cells during embryogenesis, but its role in cellular fitness has long been a mystery. Vimentin is acknowledged to play a role in cell stiffness, cell motility, and cytoplasmic organization, yet it is widely considered to be dispensable for cellular function and organismal development. Here, we show that Vimentin plays a role in cellular stress response in differentiating cells, by recruiting aggregates, stress granules, and RNA-binding proteins, directing their elimination and asymmetric partitioning. In the absence of Vimentin, pluripotent embryonic stem cells fail to differentiate properly, with a pronounced deficiency in neuronal differentiation. Our results uncover a novel function for Vimentin, with important implications for development, tissue homeostasis, and in particular, stress response.

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Section: Discussionmentioning

confidence: 73%

Vimentin protects differentiating stem cells from stress

Pattabiraman

Azad

Amen

et al. 2020

Sci Rep

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“…However, parts of the ER appear to be degraded along with the endocytic proteins. It is therefore appealing to speculate a twofold involvement of ER -first, by providing a membrane source for autophagosome biogenesis (Maeda et al, 2019;Osawa et al, 2019;Schutter et al, 2020;Valverde et al, 2019) and second, by regulating the dynamics of the END condensate, a concept recently established for processing bodies (Lee et al, 2020b). Importantly, our ultrastructural dissection provides the first view how LLPS condensates can be packed into autophagosomes, with ER at the periphery, and future experiments are needed to determine the role of the ER in this process.…”

Section: Discussionmentioning

confidence: 95%

A selective autophagy pathway for phase separated endocytic protein deposits

Wilfling

Lee

Erdmann

et al. 2020

Preprint

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“…The endoplasmic reticulum is a structurally complex organelle known to serve multiple functions, including mRNA translation, protein translocation, protein folding, posttranslational protein modifications, lipid biosynthesis, and calcium transport [69,96]. In addition, the ER contains specialized domains dedicated to interactions with other membrane organelles, such as the mitochondria and endosomes, and was recently demonstrated to participate in stress granule and processing body dynamics [97][98][99][100].…”

Section: Functional Domain Organization Of the Er Membranementioning

confidence: 99%

Quantitative Proteomics Links the LRRC59 Interactome to mRNA Translation on the ER Membrane

Hannigan

Hoffman

Thompson

et al. 2020

Molecular & Cellular Proteomics

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Protein synthesis on the endoplasmic reticulum (ER) requires the dynamic coordination of numerous cellular components. Together, resident ER membrane proteins, cytoplasmic translation factors, and both integral membrane and cytosolic RNA-binding proteins operate in concert with membrane-associated ribosomes to facilitate ER-localized translation. Little is known, however, regarding the spatial organization of ER-localized translation. This question is of growing significance as it is now known that ER-bound ribosomes contribute to secretory, integral membrane, and cytosolic protein synthesis alike. To explore this question, we utilized quantitative proximity proteomics to identify neighboring protein networks for the candidate ribosome interactors SEC61β (subunit of the protein translocase), RPN1 (oligosaccharyltransferase subunit), SEC62 (translocation integral membrane protein), and LRRC59 (ribosome binding integral membrane protein). Biotin labeling time course studies of the four BioID reporters revealed distinct labeling patterns that intensified but only modestly diversified as a function of labeling time, suggesting that the ER membrane is organized into discrete protein interaction domains. Whereas SEC61β and RPN1 reporters identified translocon-associated networks, SEC62 and LRRC59 reporters revealed divergent protein interactomes. Notably, the SEC62 interactome is enriched in redox-linked proteins and ER luminal chaperones, with the latter likely representing proximity to an ER luminal chaperone reflux pathway. In contrast, the LRRC59 interactome is highly enriched in SRP pathway components, translation factors, and ER-localized RNA-binding proteins, uncovering a functional link between LRRC59 and mRNA translation regulation. Importantly, analysis of the LRRC59 interactome by native immunoprecipitation identified similar protein and functional enrichments. Moreover, [35S]-methionine incorporation assays revealed that siRNA silencing of LRRC59 expression reduced steady state translation levels on the ER by ca. 50%, and also impacted steady state translation levels in the cytosol compartment. Collectively, these data reveal a functional domain organization for the ER and identify a key role for LRRC59 in the organization and regulation of local translation.

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Endoplasmic reticulum contact sites regulate the dynamics of membraneless organelles

Cited by 229 publications

References 45 publications

Vimentin protects differentiating stem cells from stress

Vimentin protects differentiating stem cells from stress

A selective autophagy pathway for phase separated endocytic protein deposits

Quantitative Proteomics Links the LRRC59 Interactome to mRNA Translation on the ER Membrane

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