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Integrin-based diffusion barrier separates membrane domains enabling formation of microbiostatic frustrated phagosomes
eLife ( IF 7.7 ) Pub Date : 2018-03-19 , DOI: 10.7554/elife.34798
Michelle E Maxson 1 , Xenia Naj 2 , Teresa R O'Meara 3 , Jonathan D Plumb 1 , Leah E Cowen 3 , Sergio Grinstein 1, 4, 5
Affiliation  

Candida albicans hyphae can reach enormous lengths, precluding their internalization by phagocytes. Nevertheless, macrophages engulf a portion of the hypha, generating incompletely sealed tubular phagosomes. These frustrated phagosomes are stabilized by a thick cuff of F-actin that polymerizes in response to non-canonical activation of integrins by fungal glycan. Despite their continuity, the surface and invaginating phagosomal membranes retain a strikingly distinct lipid composition. PtdIns(4,5)P2 is present at the plasmalemma but is not detectable in the phagosomal membrane, while PtdIns(3)P and PtdIns(3,4,5)P3 co-exist in the phagosomes yet are absent from the surface membrane. Moreover, endo-lysosomal proteins are present only in the phagosomal membrane. Fluorescence recovery after photobleaching revealed the presence of a diffusion barrier that maintains the identity of the open tubular phagosome separate from the plasmalemma. Formation of this barrier depends on Syk, Pyk2/Fak and formin-dependent actin assembly. Antimicrobial mechanisms can thereby be deployed, limiting the growth of the hyphae.

中文翻译:

基于整合素的扩散屏障分离膜结构域,从而形成抑菌抑制吞噬体

白色念珠菌菌丝可以达到巨大的长度,阻止它们被吞噬细胞内化。然而,巨噬细胞吞噬了一部分菌丝,产生了不完全密封的管状吞噬体。这些受挫的吞噬体通过厚厚的 F-肌动蛋白袖带稳定,该袖带聚合以响应真菌聚糖对整联蛋白的非规范激活。尽管它们具有连续性,但表面和内陷的吞噬体膜仍保留着明显不同的脂质成分。PtdIns(4,5)P2 存在于质膜但在吞噬体膜中检测不到,而 PtdIns(3)P 和 PtdIns(3,4,5)P3 共存于吞噬体中但不存在于表面膜中. 此外,内溶酶体蛋白仅存在于吞噬体膜中。光漂白后的荧光恢复揭示了扩散屏障的存在,该屏障保持了与质膜分离的开放管状吞噬体的身份。该屏障的形成取决于 Syk、Pyk2/Fak 和依赖于formin 的肌动蛋白组装。从而可以部署抗菌机制,限制菌丝的生长。
更新日期:2018-03-19
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