EMC3 coordinates surfactant protein and lipid homeostasis required for respiration

The Journal of Clinical Investigation
Xiaofang TangJ A Whitsett

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.

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Citations

Jul 4, 2019·American Journal of Physiology. Lung Cellular and Molecular Physiology·Yina DuYan Xu
Sep 2, 2020·The Journal of Clinical Investigation·Jeremy Katzen, Michael F Beers
Nov 19, 2019·Frontiers in Physiology·Juan Pablo Zuniga-Hertz, Hemal H Patel
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Nov 29, 2020·Journal of Cell Science·Ben P Phillips, Elizabeth A Miller
Nov 15, 2020·The Journal of Biological Chemistry·Georgi A GeorgievGordon W Laurie
Feb 20, 2021·Investigative Ophthalmology & Visual Science·Xiaowen CaoXiangtian Zhou
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Apr 1, 2021·Mucosal Immunology·Meina HuangXinhua Lin
May 8, 2021·The FEBS Journal·Sarah O'KeefeStephen High
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May 21, 2021·Journal of Biochemistry·Kazuhiko KawataYoshihiro Baba
Jul 3, 2021·Communications Biology·Sarah O'KeefeStephen High

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Datasets Mentioned

BETA
MR203415
GSE90969

Methods Mentioned

BETA
protein folding
PCR
transfection
co-IP
electron microscopy

Software Mentioned

ImageJ
Image Lab
BRB
AxioVision
DeSeq
Genomatix Pathway System ( GePS Pathway Analysis ( IPA ) suites
Bioconductor
ArrayTools
GenomicAlignment

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