EMC3 coordinates surfactant protein and lipid homeostasis required for respiration

Tang, Xiaofang; Snowball, John; Xu, Yan; Na, Cheng-Lun; Weaver, Timothy E.; Clair, Gérémy; Kyle, Jennifer; Zink, Erika; Ansong, Charles; Wei, Wei; Huang, Meina; Lin, Xinhua; Whitsett, Jeffrey A.

doi:10.1172/jci94152

Cited by 50 publications

(65 citation statements)

References 47 publications

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“…Protein misfolding in the ER can lead to proteotoxic stress that requires activation of the unfolded protein response (UPR) to restore homeostasis (Travers et al, 2000). Some in vivo models of EMC deficiency have reported UPR activation (Richard et al, 2013;Satoh et al, 2015;Tang et al, 2017), indicating that the EMC plays an important role in maintaining ER homeostasis. It is worth noting, however, that several studies did not observe induction of ER stress in response to EMC loss alone (Bircham et al, 2011;Lahiri et al, 2014;Shen et al, 2016).…”

Section: Emc and Er Stressmentioning

confidence: 99%

“…Loss or mutation of core EMC subunits results in embryonic lethality in organismal models. This indicates requirement of the EMC for maturation of key developmentally regulated proteins and hampers investigations into physiological roles of the EMC (Dickinson et al, 2016;Richard et al, 2013;Satoh et al, 2015;Tang et al, 2017). Yet, conditional and tissue-specific EMC subunit knockouts, as well as depletion of 'peripheral' subunits (i.e.…”

Section: Emc Links To Cellular and Organismal Functionsmentioning

confidence: 99%

Section: Emc Links To Cellular and Organismal Functionsmentioning

confidence: 99%

“…new-born pups (Tang et al, 2017). This was attributed to the collective disruption of the pulmonary surfactant system on three interconnected levels: (i) faulty proteolytic processing and trafficking of surfactant proteins B and C (SP-B and SP-C, respectively), (ii) aberrant surfactant lipid synthesis and, (iii) induction of the UPR (Tang et al, 2017). SP-B and SP-C are essential for distribution of alveolar surface lipids, and maintenance of low surface tension at the alveolar lipid-air interface (Sunde et al, 2017); but they do not contain obvious TMDs that might engage the EMC.…”

Section: Emc Links To Cellular and Organismal Functionsmentioning

confidence: 99%

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Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Volkmar

Christianson

2020

Journal of Cell Science

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Integral membrane proteins play key functional roles at organelles and the plasma membrane, necessitating their efficient and accurate biogenesis to ensure appropriate targeting and activity. The endoplasmic reticulum membrane protein complex (EMC) has recently emerged as an important eukaryotic complex for biogenesis of integral membrane proteins by promoting insertion and stability of atypical and sub-optimal transmembrane domains (TMDs). Although confirmed as a bona fide complex almost a decade ago, light is just now being shed on the mechanism and selectivity underlying the cellular responsibilities of the EMC. In this Review, we revisit the myriad of functions attributed the EMC through the lens of these new mechanistic insights, to address questions of the cellular and organismal roles the EMC has evolved to undertake.

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Section: Emc and Er Stressmentioning

confidence: 99%

Section: Emc Links To Cellular and Organismal Functionsmentioning

confidence: 99%

Section: Emc Links To Cellular and Organismal Functionsmentioning

confidence: 99%

Section: Emc Links To Cellular and Organismal Functionsmentioning

confidence: 99%

See 2 more Smart Citations

Squaring the EMC – how promoting membrane protein biogenesis impacts cellular functions and organismal homeostasis

Volkmar

Christianson

2020

Journal of Cell Science

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“…Recently, the EMC has been shown to have transmembrane domain insertase activity. 357 It is also possible that an undefined role of the EMC in lipid synthesis 358 may alter membrane protein maturation and expression. These proposed cellular functions are consistent with observed blocks of flavivirus entry and viral protein biogenesis.…”

Section: Pro-viral Host Factorsmentioning

confidence: 99%

Biochemistry and Molecular Biology of Flaviviruses

et al. 2018

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Flaviviruses, such as dengue, Japanese encephalitis, tick-borne encephalitis, West Nile, yellow fever, and Zika viruses, are critically important human pathogens that sicken a staggeringly high number of humans every year. Most of these pathogens are transmitted by mosquitos, and not surprisingly, as the earth warms and human populations grow and move, their geographic reach is increasing. Flaviviruses are simple RNA–protein machines that carry out protein synthesis, genome replication, and virion packaging in close association with cellular lipid membranes. In this review, we examine the molecular biology of flaviviruses touching on the structure and function of viral components and how these interact with host factors. The latter are functionally divided into pro-viral and antiviral factors, both of which, not surprisingly, include many RNA binding proteins. In the interface between the virus and the hosts we highlight the role of a noncoding RNA produced by flaviviruses to impair antiviral host immune responses. Throughout the review, we highlight areas of intense investigation, or a need for it, and potential targets and tools to consider in the important battle against pathogenic flaviviruses.

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