Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany; Department of Cell Biology, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA; Solomon H. Snyder Department of Neuroscience, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Department of Neurophysiology, NeuroCure Cluster of Excellence, Charité-Universitätsmedizin Berlin, Berlin, Germany; The Ohio State University College of Medicine, The Ohio State University, Columbus, OH 43210, USA.
Neuron. 2018 Jun 27;98(6):1184-1197.e6. doi: 10.1016/j.neuron.2018.06.005.
Ultrafast endocytosis generates vesicles from the plasma membrane as quickly as 50 ms in hippocampal neurons following synaptic vesicle fusion. The molecular mechanism underlying the rapid maturation of these endocytic pits is not known. Here we demonstrate that synaptojanin-1, and its partner endophilin-A, function in ultrafast endocytosis. In the absence of synaptojanin or endophilin, the membrane is rapidly invaginated, but pits do not become constricted at the base. The 5-phosphatase activity of synaptojanin is involved in formation of the neck, but 4-phosphatase is not required. Nevertheless, these pits are eventually cleaved into vesicles; within a 30-s interval, synaptic endosomes form and are resolved by clathrin-mediated budding. Then synaptojanin and endophilin function at a second step to aid with the removal of clathrin coats from the regenerated vesicles. These data together suggest that synaptojanin and endophilin can mediate membrane remodeling on a millisecond timescale during ultrafast endocytosis.
超快内吞作用在海马神经元中，突触小泡融合后，能够在 50 毫秒内迅速从质膜产生小泡。这种快速成熟的内陷小窝的分子机制尚不清楚。在这里，我们证明了突触结合蛋白-1及其伴侣衔接蛋白-A 在超快内吞作用中发挥作用。在没有突触结合蛋白或衔接蛋白的情况下，膜会迅速内陷，但小窝在底部不会变窄。突触结合蛋白的 5-磷酸酶活性参与了颈部的形成，但 4-磷酸酶不需要。尽管如此，这些小窝最终会被切割成小泡；在 30 秒的时间间隔内，突触内体形成并通过网格蛋白介导的出芽进行分离。然后，突触结合蛋白和衔接蛋白在第二步中发挥作用，有助于从再生的小泡中去除网格蛋白衣壳。这些数据共同表明，在超快内吞作用过程中，突触结合蛋白和衔接蛋白可以在毫秒时间尺度上介导膜重塑。
