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学科主题基础医学
Human Surfactant Protein A2 Gene Mutations Impair Dimmer/Trimer Assembly Leading to Deficiency in Protein Sialylation and Secretion
Song, Yi5; Fang, Guodong5; Shen, Haitao5; Li, Hui5; Yang, Wenbing5; Pan, Bing1,2,3; Huang, Guowei5; Lin, Guangyu6,7; Ma, Lian6,7; Willard, Belinda4; Gu, Jiang5; Zheng, Lemin1,2,3; Wang, Yongyu5
刊名PLOS ONE
2012-10-03
DOI10.1371/journal.pone.0046559
7期:10
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Multidisciplinary Sciences
研究领域[WOS]Science & Technology - Other Topics
关键词[WOS]ENDOPLASMIC-RETICULUM STRESS ; PRIMARY TRANSLATION PRODUCTS ; BRONCHOALVEOLAR LAVAGE ; PULMONARY-FIBROSIS ; GLYCOPROTEIN-A ; DEGRADATION ; DOMAIN ; DISEASE ; LUNG ; GLYCOSYLATION
英文摘要

Surfactant protein A2 (SP-A2) plays an essential role in surfactant metabolism and lung host defense. SP-A2 mutations in the carbohydrate recognition domain have been related to familial pulmonary fibrosis and can lead to a recombinant protein secretion deficiency in vitro. In this study, we explored the molecular mechanism of protein secretion deficiency and the subsequent biological effects in CHO-K1 cells expressing both wild-type and several different mutant forms of SP-A2. We demonstrate that the SP-A2 G231V and F198S mutants impair the formation of dimmer/trimer SP-A2 which contributes to the protein secretion defect. A deficiency in sialylation, but not N-linked glycosylation, is critical to the observed dimmer/trimer impairment-induced secretion defect. Furthermore, both mutant forms accumulate in the ER and form NP-40-insoluble aggregates. In addition, the soluble mutant SP-A2 could be partially degraded through the proteasome pathway but not the lysosome or autophagy pathway. Intriguingly, 4-phenylbutyrate acid (4-PBA), a chemical chaperone, alleviates aggregate formation and partially rescued the protein secretion of SP-A2 mutants. In conclusion, SP-A2 G231V and F198S mutants impair the dimmer/trimer assembly, which contributes to the protein sialylation and secretion deficiency. The intracellular protein mutants could be partially degraded through the proteasome pathway and also formed aggregates. The treatment of the cells with 4-PBA resulted in reduced aggregation and rescued the secretion of mutant SP-A2.

语种英语
WOS记录号WOS:000309454000055
项目编号210159 ; 2010CB912504 ; 2011CB503900 ; 30900595 ; 81170101
资助机构Key Project of Chinese Ministry of Education ; Introduction of Talents Program of Institutions of Higher Education of Guangdong Province ; "973&prime ; &prime ; National ST Major Project ; National Natural Science Foundation of China
引用统计
被引频次:4[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/59509
专题北京大学基础医学院_心血管所
北京大学基础医学院
作者单位1.Cleveland Clin, Prote Lab, Cleveland, OH 44106 USA
2.Shantou Univ Med Coll, Dept Pathol, Shantou, Guangdong, Peoples R China
3.Peking Univ Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Educ Minist, Inst Cardiovasc Sci,Sch Basic Med Sci, Beijing, Peoples R China
4.Peking Univ Hlth Sci Ctr, Key Lab Mol Cardiovasc Sci, Educ Minist, Inst Syst Biomed,Sch Basic Med Sci, Beijing, Peoples R China
5.Minist Hlth, Key Lab Cardiovasc Mol Biol & Regulatory Peptides, Beijing, Peoples R China
6.Shantou Univ Med Coll, Affiliated Hosp 2, Dept Pediat, Shantou, Guangdong, Peoples R China
7.Shantou Univ Med Coll, Affiliated Hosp 2, Translat Med Ctr, Shantou, Guangdong, Peoples R China
推荐引用方式
GB/T 7714
Song, Yi,Fang, Guodong,Shen, Haitao,et al. Human Surfactant Protein A2 Gene Mutations Impair Dimmer/Trimer Assembly Leading to Deficiency in Protein Sialylation and Secretion[J]. PLOS ONE,2012,7(10).
APA Song, Yi.,Fang, Guodong.,Shen, Haitao.,Li, Hui.,Yang, Wenbing.,...&Wang, Yongyu.(2012).Human Surfactant Protein A2 Gene Mutations Impair Dimmer/Trimer Assembly Leading to Deficiency in Protein Sialylation and Secretion.PLOS ONE,7(10).
MLA Song, Yi,et al."Human Surfactant Protein A2 Gene Mutations Impair Dimmer/Trimer Assembly Leading to Deficiency in Protein Sialylation and Secretion".PLOS ONE 7.10(2012).
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