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EMC3 coordinates surfactant protein and lipid homeostasis required for respiration
Xiaofang Tang, … , Xinhua Lin, Jeffrey A. Whitsett
Xiaofang Tang, … , Xinhua Lin, Jeffrey A. Whitsett
Published October 30, 2017
Citation Information: J Clin Invest. 2017;127(12):4314-4325. https://doi.org/10.1172/JCI94152.
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Research Article Angiogenesis Pulmonology Article has an altmetric score of 5

EMC3 coordinates surfactant protein and lipid homeostasis required for respiration

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Abstract

Adaptation to respiration at birth depends upon the synthesis of pulmonary surfactant, a lipid-protein complex that reduces surface tension at the air-liquid interface in the alveoli and prevents lung collapse during the ventilatory cycle. Herein, we demonstrated that the gene encoding a subunit of the endoplasmic reticulum membrane complex, EMC3, also known as TMEM111 (Emc3/Tmem111), was required for murine pulmonary surfactant synthesis and lung function at birth. Conditional deletion of Emc3 in murine embryonic lung epithelial cells disrupted the synthesis and packaging of surfactant lipids and proteins, impaired the formation of lamellar bodies, and induced the unfolded protein response in alveolar type 2 (AT2) cells. EMC3 was essential for the processing and routing of surfactant proteins, SP-B and SP-C, and the biogenesis of the phospholipid transport protein ABCA3. Transcriptomic, lipidomic, and proteomic analyses demonstrated that EMC3 coordinates the assembly of lipids and proteins in AT2 cells that is necessary for surfactant synthesis and function at birth.

Authors

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

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Figure 3

EMC3 is required for normal processing and trafficking of surfactant-associated proteins.

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EMC3 is required for normal processing and trafficking of surfactant-ass...
(A and B) E18.5 control and Emc3-cKO lung sections were stained for ABCA3 and proSP-B. ABCA3 staining was reduced and proSP-B increased in AT2 cells from Emc3-cKO mice. ProSP-B was abnormally present in peripheral lung saccules in Emc3-cKO mice, indicating its abnormal trafficking. (C and D) E18.5 control and Emc3-cKO lung sections were stained for proSP-C and mature SP-C (mSP-C). Both proSP-C and mSP-C accumulated in the cytoplasm and mSP-C was not secreted from Emc3-cKO AT2 cells. (E and F) E18.5 control and Emc3-cKO lung sections were stained for proSP-B, proSP-C, and LAMP-1, a marker for lysosome-related organelles. Intracellularly retained proSP-B and proSP-C colocalized with LAMP-1 in Emc3-cKO AT2 cells. (G) Western blotting of whole-lung lysates demonstrated decreased ABCA3 in Emc3-cKO lung. (H) Western blotting of whole-lung lysates showing the accumulation of proSP-B and proSP-C, and lack of mature SP-B (mSP-B) in Emc3-cKO lung. Scale bars: 50 μm.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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