The Amoebal Model for Macropinocytosis.
The Amoebal Model for Macropinocytosis.
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DOI：
10.1007/978-3-030-94004-1_3
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发表时间：
2022-01-01
影响因子：
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通讯作者：
Bretschneider, Till
中科院分区：
文献类型：
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作者：
Kay, Robert R;Lutton, Josiah;Bretschneider, Till
巨胞饮作用是一种由肌动蛋白细胞骨架驱动的相对未被探索的大规模内吞作用形式。网骨藻从质膜伸出的杯状体形成大胞饮体，然后在内-溶酶体系统中消化其内容物并吸收营养。它们利用巨胞饮作用进食，保持高的液体摄取率，使测定和实验变得容易。多年来收集的突变体鉴定巨胞饮所需的细胞骨架和信号蛋白。杯状物围绕着强烈的PIP 3、Ras和Rac信号传导的质膜结构域组织，其适当的形成也取决于RasGAP NF 1和RGBARG、PTEN、PIP 3调节的蛋白激酶Akt和SGK及其激活剂PDK 1和TORC 2、Rho蛋白以及其他有待鉴定的组分。该PIP 3结构域通过在自身周围募集SCAR/WAVE复合物的环并因此激活Arp 2/3复合物来将树突状肌动蛋白聚合引导至巨胞饮杯的延伸唇。PIP 3结构域的动力学被提出来从开始到结束形成巨胞饮杯。Ras-PI 3-激酶模块在单细胞生物中组织摄食结构的作用很可能早于其通过生长因子信号传导，这表明生长因子信号传导的进化起源。
Macropinocytosis is a relatively unexplored form of large-scale endocytosis driven by the actin cytoskeleton. Dictyostelium amoebae form macropinosomes from cups extended from the plasma membrane, then digest their contents and absorb the nutrients in the endo-lysosomal system. They use macropinocytosis for feeding, maintaining a high rate of fluid uptake that makes assay and experimentation easy. Mutants collected over the years identify cytoskeletal and signalling proteins required for macropinocytosis. Cups are organized around plasma membrane domains of intense PIP3, Ras and Rac signalling, proper formation of which also depends on the RasGAPs NF1 and RGBARG, PTEN, the PIP3-regulated protein kinases Akt and SGK and their activators PDK1 and TORC2, Rho proteins, plus other components yet to be identified. This PIP3 domain directs dendritic actin polymerization to the extending lip of macropinocytic cups by recruiting a ring of the SCAR/WAVE complex around itself and thus activating the Arp2/3 complex. The dynamics of PIP3 domains are proposed to shape macropinocytic cups from start to finish. The role of the Ras-PI3-kinase module in organizing feeding structures in unicellular organisms most likely predates its adoption into growth factor signalling, suggesting an evolutionary origin for growth factor signalling.