The resealing factor S100A11 interacts with annexins and extended synaptotagmin-1 in the course of plasma membrane wound repair.
The resealing factor S100A11 interacts with annexins and extended synaptotagmin-1 in the course of plasma membrane wound repair.
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DOI：
10.3389/fcell.2022.968164
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发表时间：
2022
影响因子：
5.5
通讯作者：
Gerke, Volker
中科院分区：
文献类型：
--
作者：
Ashraf, Arsila P. K.;Gerke, Volker
关键词：
损伤后，细胞修复其质膜在一个积极的过程，这是由Ca 2+通过伤口进入驱动。这触发了一系列Ca 2+调节事件，例如不同的Ca 2+结合蛋白易位到可能在修复过程中起作用的伤口部位。易位的蛋白质包括膜联蛋白（ANX）家族的Ca 2 +/磷脂结合蛋白和S100 A11，一种可以与ANX相互作用的EF手型Ca 2+结合蛋白。S100 A11介导PM伤口修复的分子机制仍然知之甚少，尽管它可能涉及与ANX的相互作用。在这里，使用S100 A11敲除内皮细胞和S100 A11突变体的表达，我们表明，内皮S100 A11是有效的质膜创伤修复所必需的，并通过其C-末端延伸（残基93-105）参与与ANXA 1和ANXA 2的Ca 2+依赖性相互作用。在S100 A11不存在的情况下，ANXA 2而不是ANXA 1易位到伤口基本上被抑制;然而，S100 A11敲除细胞中的修复缺陷被ANX相互作用缺陷的S100 A11突变体的异位表达所拯救，这表明S100 A11在膜伤口修复中的ANX独立作用。在寻找其他相互作用的合作伙伴，可以介导这种行动的S100 A11，我们确定了扩展synaptotagmin 1（E-Syt 1），一种蛋白质系链，调节内质网质膜接触位点。E-Syt 1在Ca 2+存在下与S100 A11结合，E-Syt 1的耗尽干扰S100 A11的伤口部位募集和适当的膜重新密封。因此，S100 A11在膜创伤修复中的作用并不完全依赖于ANX相互作用，并且Ca 2+调节的S100 A11-E-Syt 1复合物作为膜重新密封机制的尚未识别的组分起作用。
After damage, cells repair their plasma membrane in an active process that is driven by Ca2+ entering through the wound. This triggers a range of Ca2+-regulated events such as the translocation of different Ca2+-binding proteins to the wound site which likely function in the repair process. The translocated proteins include Ca2+/phospholipid binding proteins of the annexin (ANX) family and S100A11, an EF hand-type Ca2+-binding protein which can interact with ANX. The molecular mechanism by which S100A11 mediates PM wound repair remains poorly understood although it likely involves interactions with ANX. Here, using S100A11 knockout endothelial cells and expression of S100A11 mutants, we show that endothelial S100A11 is essential for efficient plasma membrane wound repair and engages in Ca2+-dependent interactions with ANXA1 and ANXA2 through its C-terminal extension (residues 93–105). ANXA2 but not ANXA1 translocation to the wound is substantially inhibited in the absence of S100A11; however, the repair defect in S100A11 knockout cells is rescued by ectopic expression of an ANX interaction-defective S100A11 mutant, suggesting an ANX-independent role of S100A11 in membrane wound repair. In search for other interaction partners that could mediate this action of S100A11 we identify extended synaptotagmin 1 (E-Syt1), a protein tether that regulates endoplasmic reticulum-plasma membrane contact sites. E-Syt1 binds to S100A11 in the presence of Ca2+ and depletion of E-Syt1 interferes with wound site recruitment of S100A11 and proper membrane resealing. Thus, the role of S100A11 in membrane wound repair does not exclusively dependent on ANX interactions and a Ca2+-regulated S100A11-E-Syt1 complex acts as a yet unrecognized component of the membrane resealing machinery.
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影响因子：
11.8
作者：
Eden ER;Sanchez-Heras E;Tsapara A;Sobota A;Levine TP;Futter CE
通讯作者：
Futter CE
DOI：
10.1016/j.bbamcr.2021.118991
发表时间：
2021-04-12
影响因子：
5.1
作者：
Ashraf, Arsila P. K.;Gerke, Volker
通讯作者：
Gerke, Volker
影响因子：
64.5
作者：
Giordano F;Saheki Y;Idevall-Hagren O;Colombo SF;Pirruccello M;Milosevic I;Gracheva EO;Bagriantsev SN;Borgese N;De Camilli P
通讯作者：
De Camilli P
影响因子：
16.6
作者：
Boye TL;Maeda K;Pezeshkian W;Sønder SL;Haeger SC;Gerke V;Simonsen AC;Nylandsted J
通讯作者：
Nylandsted J
影响因子：
16.6
作者：
Jaiswal, Jyoti K.;Lauritzen, Stine P.;Scheffer, Luana;Sakaguchi, Masakiyo;Bunkenborg, Jakob;Simon, Sanford M.;Kallunki, Tuula;Jaattela, Marja;Nylandsted, Jesper
通讯作者：
Nylandsted, Jesper