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Dynamics of Auxilin 1 and GAK in clathrin-mediated traffic
Journal of Cell Biology ( IF 7.4 ) Pub Date : 2020-01-21 , DOI: 10.1083/jcb.201908142
Kangmin He 1, 2, 3 , Eli Song 2 , Srigokul Upadhyayula 1, 2, 3 , Song Dang 2 , Raphael Gaudin 1, 2 , Wesley Skillern 2 , Kevin Bu 4 , Benjamin R Capraro 1 , Iris Rapoport 1 , Ilja Kusters 1, 2 , Minghe Ma 2 , Tom Kirchhausen 1, 2, 3
Affiliation  

Clathrin-coated vesicles lose their clathrin lattice within seconds of pinching off, through the action of the Hsc70 “uncoating ATPase.” The J- and PTEN-like domain–containing proteins, auxilin 1 (Aux1) and auxilin 2 (GAK), recruit Hsc70. The PTEN-like domain has no phosphatase activity, but it can recognize phosphatidylinositol phosphate head groups. Aux1 and GAK appear on coated vesicles in successive transient bursts, immediately after dynamin-mediated membrane scission has released the vesicle from the plasma membrane. These bursts contain a very small number of auxilins, and even four to six molecules are sufficient to mediate uncoating. In contrast, we could not detect auxilins in abortive pits or at any time during coated pit assembly. We previously showed that clathrin-coated vesicles have a dynamic phosphoinositide landscape, and we have proposed that lipid head group recognition might determine the timing of Aux1 and GAK appearance. The differential recruitment of Aux1 and GAK correlates with temporal variations in phosphoinositide composition, consistent with a lipid-switch timing mechanism.

中文翻译:

网格蛋白介导的交通中辅助蛋白 1 和 GAK 的动态

通过 Hsc70“脱壳 ATP 酶”的作用,网格蛋白包被的囊泡在夹断后几秒钟内就失去了网格蛋白晶格。含有 J 和 PTEN 样结构域的蛋白 auxilin 1 (Aux1) 和 auxilin 2 (GAK) 会招募 Hsc70。PTEN 样结构域没有磷酸酶活性,但可以识别磷脂酰肌醇磷酸头基。在动力介导的膜分裂将囊泡从质膜上释放出来后,Aux1 和 GAK 立即以连续的瞬时爆发形式出现在包被的囊泡上。这些爆发含有极少量的辅助素,甚至四到六个分子就足以介导脱壳。相比之下,我们无法在流产的坑中或在包被的坑组装过程中的任何时间检测到辅助素。我们之前表明,网格蛋白包被的囊泡具有动态的磷酸肌醇景观,并且我们提出脂质头基识别可能决定 Aux1 和 GAK 出现的时间。Aux1 和 GAK 的差异募集与磷酸肌醇组成的时间变化相关,与脂质开关计时机制一致。
更新日期:2020-01-21
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