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冠蛋白1三聚化对于保护巨噬细胞内的致病性分枝杆菌免受溶酶体转运至关重要。

Coronin 1 trimerization is essential to protect pathogenic mycobacteria within macrophages from lysosomal delivery.

作者信息

BoseDasgupta Somdeb, Pieters Jean

机构信息

Biozentrum, University of Basel, Switzerland.

Biozentrum, University of Basel, Switzerland.

出版信息

FEBS Lett. 2014 Nov 3;588(21):3898-905. doi: 10.1016/j.febslet.2014.08.036. Epub 2014 Sep 12.

DOI:10.1016/j.febslet.2014.08.036
PMID:25217836
Abstract

Coronin 1 is a member of the evolutionarily conserved coronin protein family. Coronin proteins are characterized by the presence of a central WD repeat and a C-terminal coiled coil that in coronin 1 is responsible for trimerization. Coronin 1 was identified as a host protein protecting intracellularly residing mycobacteria from degradation by activating the Ca(2+)/calcineurin pathway but whether or not trimerization is essential for this function remains unknown. We here show that trimerization is essential to promote mycobacterial survival within macrophages and activate calcineurin. Furthermore, macrophage activation that induces serine-phosphorylation on coronin 1 resulted in coronin 1 monomerization. These results suggest that modulation of coronin 1 oligomerization is an effective way to determine the outcome of a mycobacterial infection in macrophages.

摘要

冠蛋白1是进化上保守的冠蛋白家族的成员。冠蛋白的特征是存在一个中央WD重复序列和一个C末端卷曲螺旋,在冠蛋白1中,该卷曲螺旋负责三聚化。冠蛋白1被鉴定为一种宿主蛋白,它通过激活Ca(2+)/钙调神经磷酸酶途径来保护细胞内的分枝杆菌不被降解,但三聚化对于该功能是否必不可少仍不清楚。我们在此表明,三聚化对于促进分枝杆菌在巨噬细胞内存活和激活钙调神经磷酸酶至关重要。此外,诱导冠蛋白1丝氨酸磷酸化的巨噬细胞激活导致冠蛋白1单体化。这些结果表明,调节冠蛋白1的寡聚化是决定巨噬细胞中分枝杆菌感染结果的有效方式。

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