The investigation to Dynamin-1 for new antidepressats binding protein

动力蛋白(Dyn)1在突触小泡的循环中发挥作用，从而影响神经系统的功能。选择性5-羟色胺再摄取抑制剂(SSRI)氟伏沙明可能与L-磷脂酰丝氨酸(PS)竞争结合动力蛋白I(Dyn 1)GTP酶的pleckstrin同源结构域。另一方面，舍曲林对GTP和PS都是一种混合型抑制剂。在体外实验中，舍曲林对GTP和L-α-磷脂酰丝氨酸(PS)都是Dyn-1的混合型抑制剂，提示舍曲林可能通过抑制Dyn-1 GTP酶来调节突触小泡内皮细胞的神经递质转运。GTP酶分析显示舍曲林对Dyn-2和Dyn-1均有抑制作用。因此，舍曲林对细胞内吞作用的影响是由Dyn-2介导的，至少在HeLa细胞中是这样，在表达Dyn-2的细胞系中也是由Dyn-1介导的。此外，舍曲林抑制转铁蛋白(Tf)摄取的机制与表达GTP结合缺陷突变体dyn 1 K44A的细胞不同。

Dynamin (Dyn) 1 plays a role in recycling of synaptic vesicles, and thus in nervous system function. Fluvoxamine , a selective serotonin reuptake inhibitor (SSRI),may compete with L-phosphatidylserine (PS) for binding to the pleckstrin homology domain of dynamin I (Dyn 1) GTPase. On the other hand, sertraline was a mixed type inhibitor with respect to both GTP and PS. We showed that sertraline is a mixed-type inhibitorof Dyn 1 with respect to both GTP and L-a-phosphatidyl-L-serine (PS) in vitro, and we suggested that it may regulate the neurotransmitter transport by modulating synaptic vesicle endocytos is via inhibition of Dyn 1 GTPase. GTPase assay showed that sertraline inhibited Dyn 2 as well as Dyn 1. Therefore, the effect of sertraline on endocytosis was mediated by Dyn 2, at least in HeLa cells, as well as by Dyn 1 in cell lines that express it. Moreover, the inhibition mechanism of transferrin (Tf) uptake by sertraline differed from that in cells expressing Dyn 1 K44A, a GTP binding-defective variant.