Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling.
Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling.
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DOI：
10.1126/science.1253768
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发表时间：
2014-06-27
期刊：
影响因子：
--
通讯作者：
Chavrier P
中科院分区：
文献类型：
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作者：
Boissan M;Montagnac G;Shen Q;Griparic L;Guitton J;Romao M;Sauvonnet N;Lagache T;Lascu I;Raposo G;Desbourdes C;Schlattner U;Lacombe ML;Polo S;van der Bliek AM;Roux A;Chavrier P
发动蛋白超家族分子马达使用三磷酸鸟苷（GTP）作为膜重塑事件的能量来源。我们发现，通过三磷酸腺苷（ATP）驱动的鸟苷二磷酸（GDP）转化产生GTP的核苷二磷酸激酶（NDPKs）NM 23-H1/H2的敲低，抑制动力蛋白介导的内吞作用。NM 23-H1/H2定位于网格蛋白包被的凹陷处，并与发动蛋白的富含脯氨酸的结构域相互作用。在体外，NM 23-H1/H2被募集到发动蛋白诱导的小管，刺激发动蛋白上的GTP负载，并在ATP和GDP存在下触发裂变。NM 23-H4是一种线粒体特异性NDPK，与线粒体动力蛋白样OPA 1共定位，参与线粒体内膜融合并增加OPA 1上的GTP负载。与OPA 1功能丧失类似，沉默NM 23-H4而非NM 23-H1/H2导致线粒体片段化，反映融合缺陷。因此，NDPKs与发动蛋白相互作用并为发动蛋白提供GTP，使这些马达蛋白以高热力学效率工作。
Dynamin superfamily molecular motors use guanosine triphosphate (GTP) as a source of energy for membrane-remodeling events. We found that knockdown of nucleoside diphosphate kinases (NDPKs) NM23-H1/H2, which produce GTP through adenosine triphosphate (ATP)–driven conversion of guanosine diphosphate (GDP), inhibited dynamin-mediated endocytosis. NM23-H1/H2 localized at clathrin-coated pits and interacted with the proline-rich domain of dynamin. In vitro, NM23-H1/H2 were recruited to dynamin-induced tubules, stimulated GTP-loading on dynamin, and triggered fission in the presence of ATP and GDP. NM23-H4, a mitochondria-specific NDPK, colocalized with mitochondrial dynamin-like OPA1 involved in mitochondria inner membrane fusion and increased GTP-loading on OPA1. Like OPA1 loss of function, silencing of NM23-H4 but not NM23-H1/H2 resulted in mitochondrial fragmentation, reflecting fusion defects. Thus, NDPKs interact with and provide GTP to dynamins, allowing these motor proteins to work with high thermodynamic efficiency.