Dictyostelium discoideum nucleoside diphosphate kinase C plays a negative regulatory role in phagocytosis, macropinocytosis and exocytosis.

Dictyostelium discoideum nucleoside diphosphate kinase C plays a negative regulatory role in phagocytosis, macropinocytosis and exocytosis.
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dictyostelium Discoideum核苷双磷酸激酶C在吞噬作用,大细胞增多症和胞吐作用中起负调节作用。

DOI:
10.1371/journal.pone.0026024
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发表时间:
2011
期刊:
影响因子:
3.7
通讯作者:
Fisher PR
Fisher PR
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Annesley SJ;Bago R;Bosnar MH;Filic V;Marinović M;Weber I;Mehta A;Fisher PR

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核苷二磷酸激酶 (NDPK) 是普遍存在的磷酸转移酶,负责产生除 ATP 之外的大部分核苷三磷酸。这一作用对于核酸和蛋白质的合成以及糖和脂质的代谢很重要。除了这种管家作用之外,NDPK 已被证明在不同的细胞过程中具有许多调节功能,包括增殖和内吞作用。尽管该蛋白已被证明在网格蛋白和动力介导的小胞饮作用中具有积极的调节作用,但其在巨胞饮作用和吞噬作用中的作用尚未被研究。 NDPK 的额外非管家作用通常与酶活性无关,但取决于蛋白质的表达水平。在本研究中,我们通过反义抑制和过表达改变了模型真核生物盘基网柄菌中 NDPK 的表达水平。我们证明 NDPK 水平影响生长、胞吞作用和胞吐作用。特别是,我们发现盘基网柄菌 NDPK 负调节内吞作用,与高等真核生物中发现的正调节作用相反。这可以通过不同系统中研究的内吞作用类型的差异来解释——盘基网柄菌属中的吞噬作用和巨胞饮作用与哺乳动物细胞中的小胞饮作用相比。这是首次报道 NDPK 在调节巨胞饮作用和吞噬作用中的作用,前者是巨噬细胞、树突状细胞和暴露于生长因子的其他(非树突状)细胞的主要液相摄取机制。
Nucleoside diphosphate kinases (NDPKs) are ubiquitous phosphotransfer enzymes responsible for producing most of the nucleoside triphosphates except for ATP. This role is important for the synthesis of nucleic acids and proteins and the metabolism of sugars and lipids. Apart from this housekeeping role NDPKs have been shown to have many regulatory functions in diverse cellular processes including proliferation and endocytosis. Although the protein has been shown to have a positive regulatory role in clathrin- and dynamin-mediated micropinocytosis, its roles in macropinocytosis and phagocytosis have not been studied. The additional non-housekeeping roles of NDPK are often independent of enzyme activity but dependent on the expression level of the protein. In this study we altered the expression level of NDPK in the model eukaryotic organism Dictyostelium discoideum through antisense inhibition and overexpression. We demonstrate that NDPK levels affect growth, endocytosis and exocytosis. In particular we find that Dictyostelium NDPK negatively regulates endocytosis in contrast to the positive regulatory role identified in higher eukaryotes. This can be explained by the differences in types of endocytosis that have been studied in the different systems - phagocytosis and macropinocytosis in Dictyostelium compared with micropinocytosis in mammalian cells. This is the first report of a role for NDPK in regulating macropinocytosis and phagocytosis, the former being the major fluid phase uptake mechanism for macrophages, dendritic cells and other (non dendritic) cells exposed to growth factors.
DOI: 10.1006/plas.1997.1326
发表时间: 1998-01-01
期刊: PLASMID
影响因子: 2.6
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