Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.
Dynamin 1xA interacts with Endophilin A1 via its spliced long C-terminus for ultrafast endocytosis.
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Dynamin 1xA 通过其剪接的长 C 末端与 Endophilin A1 相互作用，实现超快内吞作用。
DOI：
10.1101/2023.09.21.558797
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Robinson,PhillipJ
中科院分区：
文献类型：
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作者：
Imoto,Yuuta;Xue,Jing;Luo,Lin;Raychaudhuri,Sumana;Itoh,Kie;Ma,Ye;Craft,GeorgeE;Kwan,AnnH;Mackay,JoelP;Ha,Taekjip;Watanabe,Shigeki;Robinson,PhillipJ
发动蛋白1介导脑内吞突触囊泡的分裂，并具有两个主要的剪接变体Dyn 1xA和Dyn 1xB，除了Dyn 1xA的延伸C末端区域外，它们几乎相同。尽管有类似的一组结合伙伴，只有Dyn 1xA是丰富的内吞区，并加速囊泡分裂过程中超快内吞。在这里，我们报告说，Dyn 1xA通过优先结合到Endophilin A1通过一个新定义的结合位点在其长的C-末端尾部延伸实现这一定位。Endophilin A1以比先前报道的位点更高的亲和力结合该位点，并且亲和力由Dyn 1xA尾内但结合位点外的氨基酸决定。这种相互作用由Dyn 1xA变体特异性的两个丝氨酸残基的磷酸化状态调节。Dyn 1xA和Endophilin A1共定位在活性区附近的斑块中，并且破坏Endophilin A与长尾结合的突变导致Dyn 1xA在超快内吞作用期间在质膜上的错误定位和停滞的内吞凹陷。总之，这些数据表明，超快内吞作用的特异性是由磷酸化调节的相互作用的Endophilin A1与Dyn 1xA的C-末端延伸。
Dynamin 1 mediates fission of endocytic synaptic vesicles in the brain and has two major splice variants, Dyn1xA and Dyn1xB, which are nearly identical apart from the extended C-terminal region of Dyn1xA. Despite a similar set of binding partners, only Dyn1xA is enriched at endocytic zones and accelerates vesicle fission during ultrafast endocytosis. Here, we report that Dyn1xA achieves this localization by preferentially binding to Endophilin A1 through a newly defined binding site within its long C-terminal tail extension. Endophilin A1 binds this site at higher affinity than the previously reported site, and the affinity is determined by amino acids within the Dyn1xA tail but outside the binding site. This interaction is regulated by the phosphorylation state of two serine residues specific to the Dyn1xA variant. Dyn1xA and Endophilin A1 colocalize in patches near the active zone, and mutations disrupting Endophilin A binding to the long tail cause Dyn1xA mislocalization and stalled endocytic pits on the plasma membrane during ultrafast endocytosis. Together, these data suggest that the specificity for ultrafast endocytosis is defined by the phosphorylation-regulated interaction of Endophilin A1 with the C-terminal extension of Dyn1xA.