Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.
Dynein Clusters into Lipid Microdomains on Phagosomes to Drive Rapid Transport toward Lysosomes.
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DOI：
10.1016/j.cell.2015.12.054
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发表时间：
2016-02-11
期刊：
影响因子：
64.5
通讯作者：
Mallik R
中科院分区：
文献类型：
--
作者：
Rai A;Pathak D;Thakur S;Singh S;Dubey AK;Mallik R
不同的细胞过程是由马达蛋白驱动的，马达蛋白被招募到脂质膜上并在脂质膜上产生力。令人惊讶的是，人们对膜如何控制来自马达的力以及这如何影响特定的细胞功能知之甚少。在这里，我们表明，动力蛋白电机物理集群成微域上的吞噬体膜，因为它在细胞内成熟。这样的几何重组允许一个簇内的许多动力蛋白在单个微管上产生协同力。这导致吞噬体向微管负末端的快速定向运输，可能促进吞噬溶酶体融合和病原体降解。我们发现，脂磷酸聚糖，参与免疫逃避杜氏利什曼原虫的主要分子，抑制吞噬体运动破坏集群，因此动力蛋白的合作力的产生。这些发现似乎与通过靶向吞噬体上的脂质微区来防止吞噬体-溶酶体融合的几种病原体有关。动力蛋白在吞噬体上成熟时聚集成脂质微区聚集允许许多动力蛋白同时接触单个微管现在可以产生大的协同力将吞噬体运输到溶酶体利什曼原虫脂磷酸聚糖破坏微区并抑制这种运输动力蛋白马达在吞噬体膜上物理聚集成脂筏，因为它在细胞内成熟。簇中的几何组织增加了力的产生，并允许许多马达合作以驱动吞噬体的快速运输，这是消除许多细胞内病原体所需的过程。
Diverse cellular processes are driven by motor proteins that are recruited to and generate force on lipid membranes. Surprisingly little is known about how membranes control the force from motors and how this may impact specific cellular functions. Here, we show that dynein motors physically cluster into microdomains on the membrane of a phagosome as it matures inside cells. Such geometrical reorganization allows many dyneins within a cluster to generate cooperative force on a single microtubule. This results in rapid directed transport of the phagosome toward microtubule minus ends, likely promoting phagolysosome fusion and pathogen degradation. We show that lipophosphoglycan, the major molecule implicated in immune evasion of Leishmania donovani, inhibits phagosome motion by disrupting the clustering and therefore the cooperative force generation of dynein. These findings appear relevant to several pathogens that prevent phagosome-lysosome fusion by targeting lipid microdomains on phagosomes. Dynein clusters into lipid microdomains on the phagosome as it matures Clustering allows many dyneins to simultaneously contact a single microtubule Large cooperative forces can now be generated to transport phagosomes to lysosomes Leishmania lipophosphoglycans disrupt microdomains and inhibit this transport Dynein motors physically cluster into lipid rafts on the membrane of a phagosome as it matures inside the cell. The geometric organization in clusters increases the generation of force and allows many motors to cooperate to drive fast transport of the phagosome, a process required for elimination of many intracellular pathogens.