Human surfactant protein A2 gene mutations impair dimmer/trimer assembly leading to deficiency in protein sialylation and secretion.
Human surfactant protein A2 gene mutations impair dimmer/trimer assembly leading to deficiency in protein sialylation and secretion.
复制标题
人类表面活性剂蛋白 A2 基因突变损害二聚体/三聚体组装，导致蛋白质唾液酸化和分泌缺陷
DOI：
10.1371/journal.pone.0046559
复制
发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Wang Y
中科院分区：
文献类型：
--
作者：
Song Y;Fang G;Shen H;Li H;Yang W;Pan B;Huang G;Lin G;Ma L;Willard B;Gu J;Zheng L;Wang Y
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.
登录
查看更多内容
DOI：
10.1164/ajrccm/144.1.160
发表时间：
1991-07-01
期刊：
AMERICAN REVIEW OF RESPIRATORY DISEASE
影响因子：
--
作者：
MCCORMACK, FX;KING, TE;MASON, RJ
通讯作者：
MASON, RJ
影响因子：
4.8
作者：
Maitra, Meenakshi;Wang, Yongyu;Garcia, Christine Kim
通讯作者：
Garcia, Christine Kim
DOI：
10.1152/ajplung.00025.2007
发表时间：
2007-09-01
影响因子：
4.9
作者：
Mulugeta, Surafel;Maguire, Jean Ann;Beers, Michael F.
通讯作者：
Beers, Michael F.
DOI：
10.1016/0167-4889(88)90073-0
发表时间：
1988-04-25
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
OREILLY, MA;NOGEE, L;WHITSETT, JA
通讯作者：
WHITSETT, JA
DOI：
10.1016/0167-4838(86)90073-7
发表时间：
1986-02-14
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
WEAVER, TE;HULL, WM;WHITSETT, JA
通讯作者：
WHITSETT, JA