Tubular lysosomes harbor active ion gradients and poise macrophages for phagocytosis.
Tubular lysosomes harbor active ion gradients and poise macrophages for phagocytosis.
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DOI：
10.1073/pnas.2113174118
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发表时间：
2021-10-12
影响因子：
11.1
通讯作者：
Krishnan Y
中科院分区：
文献类型：
--
作者：
Suresh B;Saminathan A;Chakraborty K;Zajac M;Cui C;Becker L;Krishnan Y
溶酶体是细胞器，也是细胞信号中枢。它们调节从抗原呈递到自噬的功能。在饥饿或发炎的免疫细胞中，球形溶酶体可以自发地伸长成小管。我们描述了一种基于DNA的试剂，表示都铎，微管在巨噬细胞中的溶酶体不触发免疫反应或自噬。化学成像显示，管状溶酶体不同于囊泡的pH值，钙，和蛋白水解活性。Tudor揭示了管状溶酶体的作用在于它们增强静息巨噬细胞中的MMP 9分泌和吞噬作用。在静止的免疫细胞中微管化溶酶体而不使其饥饿或发炎的能力可能有助于揭示对管状溶酶体功能的新见解。溶酶体采取动态的管状状态，调节抗原呈递、吞噬体分解和自噬。通过诱导自噬或通过激活免疫细胞来研究管状溶酶体，这两种方法都导致溶酶体基因表达不同于静息状态的细胞状态。因此，确定溶酶体在微管上获得的可以驱动其功能的生化特性一直是具有挑战性的。在这里，我们描述了一个基于DNA的组装，微管在巨噬细胞中的溶酶体，而不激活它们。单溶酶体分辨率的蛋白水解活性图显示，管状溶酶体降解较少，并显示近端至远端管腔pH和Ca2+梯度。这种梯度已经被预测到，但以前从未观察到。我们确定了肾小管溶酶体在促进吞噬作用和激活MMP 9中的作用。在不饥饿或激活免疫细胞的情况下使溶酶体微管化的能力可能有助于揭示管状溶酶体的新作用。
Lysosomes are organelles that also act as cell-signaling hubs. They regulate functions ranging from antigen presentation to autophagy. Spherical lysosomes can spontaneously elongate into tubules in starving or inflamed immune cells. We describe a DNA-based reagent, denoted Tudor, that tubulates lysosomes in macrophages without triggering either an immune response or autophagy. Chemical imaging revealed that tubular lysosomes differ from vesicular ones in terms of their pH, calcium, and proteolytic activity. Tudor revealed a role for tubular lysosomes in that they enhance MMP9 secretion and phagocytosis in resting macrophages. The ability to tubulate lysosomes in resting immune cells without starving or inflaming them may help reveal new insights into how tubular lysosomes function. Lysosomes adopt dynamic, tubular states that regulate antigen presentation, phagosome resolution, and autophagy. Tubular lysosomes are studied either by inducing autophagy or by activating immune cells, both of which lead to cell states where lysosomal gene expression differs from the resting state. Therefore, it has been challenging to pinpoint the biochemical properties lysosomes acquire upon tubulation that could drive their functionality. Here we describe a DNA-based assembly that tubulates lysosomes in macrophages without activating them. Proteolytic activity maps at single-lysosome resolution revealed that tubular lysosomes were less degradative and showed proximal to distal luminal pH and Ca2+ gradients. Such gradients had been predicted but never previously observed. We identify a role for tubular lysosomes in promoting phagocytosis and activating MMP9. The ability to tubulate lysosomes without starving or activating immune cells may help reveal new roles for tubular lysosomes.
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影响因子：
3.7
作者：
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通讯作者：
Shaw L
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影响因子：
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作者：
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