An N-terminally acetylated Arf-like GTPase is localised to lysosomes and affects their motility
An N-terminally acetylated Arf-like GTPase is localised to lysosomes and affects their motility
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DOI：
10.1242/jcs.02958
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发表时间：
2006-04-15
影响因子：
4
通讯作者：
Munro, S
中科院分区：
文献类型：
--
作者：
Hofmann, I;Munro, S
Arf和Rab家族的小gtpase在亚细胞细胞器的功能中起着关键作用。每个GTPase通常只存在于一个隔室中，因此，它们赋予许多细胞内过程的细胞器特异性。然而，到目前为止，还没有证据表明特异的gtp酶存在于溶酶体上。在这里，我们报道了两个密切相关的人类类arf gtpase， Arl8a和Arl8b（也称为Arl10b/c和Gie1/2），定位于哺乳动物细胞中的溶酶体，而果蝇细胞中的单一同源物具有相似的位置。通常，Arf和Arl蛋白的膜结合是由n端肉豆醇基和n端两性螺旋介导的，后者在GTPase激活后插入脂质双分子层。Arl8a和Arl8b没有n端肉豆肉酰化位点，我们发现Arl8b是n端乙酰化的，乙酰化的蛋氨酸是其溶酶体定位所必需的。Arl8a或Arl8b的过表达导致溶酶体向细胞周围的微管依赖性重新分布。活细胞成像显示溶酶体更频繁地向细胞外周移动和远离细胞外周移动，这表明Arl8a和Arl8b是溶酶体运输的积极调节因子。
Small GTPases of the Arf and Rab families play key roles in the function of subcellular organelles. Each GTPase is usually found on only one compartment and, hence, they confer organelle specificity to many intracellular processes. However, there has so far been little evidence for specific GTPases present on lysosomes. Here, we report that two closely related human Arf-like GTPases, Arl8a and Arl8b (also known as Arl10b/c and Gie1/2), localise to lysosomes in mammalian cells, with the single homologue in Drosophila cells having a similar location. Conventionally, membrane binding of Arf and Arl proteins is mediated by both an N-terminal myristoyl group and an N-terminal amphipathic helix that is inserted into the lipid bilayer upon activation of the GTPase. Arl8a and Arl8b do not have N-terminal myristoylation sites, and we find that Arl8b is instead N-terminally acetylated, and an acetylated methionine is necessary for its lysosomal localization. Overexpression of Arl8a or Arl8b results in a microtubuledependent redistribution of lysosomes towards the cell periphery. Live cell imaging shows that lysosomes move more frequently both toward and away from the cell periphery, suggesting a role for Arl8a and Arl8b as positive regulators of lysosomal transport.