CLIPA7 Exhibits Pleiotropic Roles in the Anopheles gambiae Immune Response.
CLIPA7 Exhibits Pleiotropic Roles in the Anopheles gambiae Immune Response.
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DOI：
10.1159/000526486
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发表时间：
2023
影响因子：
5.3
通讯作者：
Osta, Mike A.
中科院分区：
文献类型：
--
作者：
Zakhia, Renee;Osta, Mike A.
剪切结构域丝氨酸蛋白酶和剪切结构域丝氨酸蛋白酶同源物（cSPHs）是驱动黑化反应的丝氨酸蛋白酶级联的关键组分。尽管缺乏催化活性，cSPHs在调节黑色素化中发挥着重要作用，但它们在这些级联反应内外催化的功能谱尚未完全了解。除了它们作为PPO激活的辅因子的经典作用外，我们先前已经揭示了在疟疾媒介冈比亚按蚊的免疫应答中，这些cSPH的功能和分子组织的前所未有的复杂性。在此，我们又增加了另一个维度来支持cSPH对蚊子免疫的贡献的复杂作用，通过显示CLIPA7，扩展的cSPH家族的一个成员，定义了cSPH网络中的一个新分支，该分支对大肠杆菌而不是疟原虫或革兰氏阳性细菌的黑化是必不可少的。尽管CLIPA7对革兰氏阳性菌的黑化是可分配的，但我们表明，CLIPA7是清除金黄色葡萄球菌全身感染所必需的。CLIPA7由血细胞产生并与活大肠杆菌的表面结合。coli和革兰氏阳性菌S.金黄色葡萄球菌细胞以及与那些黑化的细胞。基于该基因的RNAi表型及其在A.我们认为CLIPA7在蚊子免疫中具有多效性作用，其作用范围超出了对黑色素化和微生物清除的调节。
Clip domain serine proteases and clip domain serine protease homologs (cSPHs) are key components of serine protease cascades that drive the melanization response. Despite lacking catalytic activity, cSPHs play essential roles in regulating melanization, but the spectrum of functions they catalyze within and outside these cascades is not fully understood. Aside from their classical role as cofactors for PPO activation, we have previously revealed an unprecedented complexity in the function and molecular organization of these cSPHs in the immune response of the malaria vector Anopheles gambiae. Here, we add yet another dimension to the complex roles underpinning the contributions of cSPHs to mosquito immunity by showing that CLIPA7, a member of the expanded cSPH family, defines a novel branch within the cSPH network that is essential for the melanization of Escherichia coli but not Plasmodium ookinetes or Gram-positive bacteria. Despite its dispensability for the melanization of Gram-positive bacteria, we show that CLIPA7 is required for the clearance of systemic infections with Staphylococcus aureus. CLIPA7 is produced by hemocytes and associates with the surfaces of live E. coli and S. aureus cells in vivo as well as with those of melanized cells. Based on its RNAi phenotypes and its unique domain architecture among A. gambiae cSPHs including the presence of an RGD motif, we propose that CLIPA7 exhibits pleiotropic roles in mosquito immunity that extend beyond the regulation of melanization to microbial clearance.
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影响因子：
6.7
作者：
Dong Y;Aguilar R;Xi Z;Warr E;Mongin E;Dimopoulos G
通讯作者：
Dimopoulos G
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2.7
作者：
HAYASHI, T;NAGAI, Y
通讯作者：
NAGAI, Y
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作者：
Dong, Yuemei;Taylor, Harry E;Dimopoulos, George
通讯作者：
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影响因子：
3.2
作者：
Kamareddine L;Fan Y;Osta MA;Keyhani NO
通讯作者：
Keyhani NO
影响因子：
32.4
作者：
Frolet, Cecile;Thoma, Martine;Levashina, Elena A.
通讯作者：
Levashina, Elena A.