Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP.

Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP. Research Abstract Details 

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Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP. Abstract Text:

N Mimura,H Hamada,M Kashio,H Jin,Y Toyama,K Kimura,M Iida,S Goto,H Saisho,K Toshimori,H Koseki,T Aoe,N Mimura,H Hamada,M Kashio,H Jin,Y Toyama,K Kimura,M Iida,S Goto,H Saisho,K Toshimori,H Koseki,T Aoe,

Accumulation of misfolded proteins in the endoplasmic reticulum (ER) induces the unfolded protein response (UPR), which alleviates protein overload in the secretory pathway. Although the UPR is activated under diverse pathological conditions, its physiological role during development and in adulthood has not been fully elucidated. Binding immunoglobulin protein (BiP) is an ER chaperone, which is central to ER function. We produced knock-in mice expressing a mutant BiP lacking the retrieval sequence to cause a defect in ER function without completely eliminating BiP. In embryonic fibroblasts, the UPR compensated for mutation of BiP. However, neonates expressing mutant BiP suffered respiratory failure due to impaired secretion of pulmonary surfactant by alveolar type II epithelial cells. Expression of surfactant protein (SP)-C was reduced and the lamellar body was malformed, indicating that BiP plays a critical role in the biosynthesis of pulmonary surfactant. Because pulmonary surfactant requires extensive post-translational processing in the secretory pathway, these findings suggest that in secretory cells, such as alveolar type II cells, the UPR is essential for managing the normal physiological ER protein overload that occurs during development. Moreover, failure of this adaptive mechanism may increase pulmonary susceptibility to environmental insults, such as hypoxia and ischemia, ultimately leading to neonatal respiratory failure.

Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP. Publishing Authors By Initials

N Mimura,H Hamada,M Kashio,H Jin,Y Toyama,K Kimura,M Iida,S Goto,H Saisho,K Toshimori,H Koseki,T Aoe,N Mimura,H Hamada,M Kashio,H Jin,Y Toyama,K Kimura,M Iida,S Goto,H Saisho,K Toshimori,H Koseki,T Aoe,

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Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cell death and differentiation

VOLUME: 14

Page Numbers: 1475-85

Journal Abbreviation: Cell Death Differ.

ISSN: 1350-9047

DAY: 20

MONTH: 04

YEAR: 2007

Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP. Information

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LANGUAGE: eng

NlmUniqueID: 9437445

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Grant and Affiliation Information for Aberrant quality control in the endoplasmic reticulum impairs the biosynthesis of pulmonary surfactant in mice expressing mutant BiP.

AFFILIATION: Department of Anesthesiology, Chiba University Graduate School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba City, Chiba, Japan.

Country: England

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MEDLINETA: Cell Death Differ

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