Sec22b Is a Negative Regulator of Phagocytosis in Macrophages
Sec22b Is a Negative Regulator of Phagocytosis in Macrophages
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DOI：
10.1091/mbc.e09-03-0241
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发表时间：
2009-10-15
影响因子：
3.3
通讯作者：
Wada, Ikuo
中科院分区：
文献类型：
--
作者：
Hatsuzawa, Kiyotaka;Hashimoto, Hitoshi;Wada, Ikuo
内质网（ER）被认为是吞噬体形成的膜供体。为了支持这一点，我们以前已经表明，突触融合蛋白18，ER定位的SNARE蛋白的表达水平，与吞噬活性。为了进一步了解ER参与吞噬作用，我们将重点放在Sec 22 b上，Sec 22 b是另一种也在吞噬体膜上发现的ER定位的SNARE蛋白。与突触融合蛋白18的作用形成鲜明对比的是，我们在此报告，在稳定表达mVenus标记的Sec 22 b的J774巨噬细胞中，吞噬作用几乎被消除，而不影响Fc受体或其他与吞噬作用相关的膜蛋白的细胞表面表达。相反，当内源性Sec 22 b表达被抑制时，亲本J774细胞的吞噬能力增加。Sec 22 b的结构域分析表明，R-SNARE基序，与syntaxin 18和/或D12形成SNARE复合物的选择性结构域，负责抑制吞噬作用。这些结果强烈支持ER介导的吞噬作用模型，并表明Sec 22 b是巨噬细胞中吞噬作用的负调节剂，最有可能通过调节吞噬作用部位的游离突触融合蛋白18和/或D12的水平。
The endoplasmic reticulum (ER) is proposed to be a membrane donor for phagosome formation. In support of this, we have previously shown that the expression level of syntaxin 18, an ER-localized SNARE protein, correlates with phagocytosis activity. To obtain further insights into the involvement of the ER in phagocytosis we focused on Sec22b, another ER-localized SNARE protein that is also found on phagosomal membranes. In marked contrast to the effects of syntaxin 18, we report here that phagocytosis was nearly abolished in J774 macrophages stably expressing mVenus-tagged Sec22b, without affecting the cell surface expression of the Fc receptor or other membrane proteins related to phagocytosis. Conversely, the capacity of the parental J774 cells for phagocytosis was increased when endogenous Sec22b expression was suppressed. Domain analyses of Sec22b revealed that the R-SNARE motif, a selective domain for forming a SNARE complex with syntaxin18 and/or D12, was responsible for the inhibition of phagocytosis. These results strongly support the ER-mediated phagocytosis model and indicate that Sec22b is a negative regulator of phagocytosis in macrophages, most likely by regulating the level of free syntaxin 18 and/or D12 at the site of phagocytosis.