Anne Christine, Gasnier Bruno
Université Paris Descartes, Sorbonne Paris Cité, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8192, Centre Universitaire des Saints-Pères, Paris, France.
Université Paris Descartes, Sorbonne Paris Cité, Centre National de la Recherche Scientifique, Unité Mixte de Recherche 8192, Centre Universitaire des Saints-Pères, Paris, France.
Curr Top Membr. 2014;73:149-74. doi: 10.1016/B978-0-12-800223-0.00003-7.
Secondary transporters driven by a V-type H⁺-ATPase accumulate nonpeptide neurotransmitters into synaptic vesicles. Distinct transporter families are involved depending on the neurotransmitter. Monoamines and acetylcholine on the one hand, and glutamate and ATP on the other hand, are accumulated by SLC18 and SLC17 transporters, respectively, which belong to the major facilitator superfamily (MFS). GABA and glycine accumulate through a common SLC32 transporter from the amino acid/polyamine/organocation (APC) superfamily. Although crystallographic structures are not yet available for any vesicular transporter, homology modeling studies of MFS-type vesicular transporters based on distantly related bacterial structures recently provided significant advances, such as the characterization of substrate-binding pockets or the identification of spatial clusters acting as hinge points during the alternating-access cycle. However, several basic issues, such as the ion stoichiometry of vesicular amino acid transporters, remain unsettled.
由V型H⁺-ATP酶驱动的次级转运体将非肽类神经递质积累到突触小泡中。根据神经递质的不同，涉及不同的转运体家族。一方面，单胺类和乙酰胆碱，另一方面，谷氨酸和ATP，分别由属于主要易化子超家族（MFS）的SLC18和SLC17转运体积累。GABA和甘氨酸通过来自氨基酸/多胺/有机阳离子（APC）超家族的共同SLC32转运体积累。尽管尚未获得任何囊泡转运体的晶体结构，但最近基于远缘相关细菌结构对MFS型囊泡转运体进行的同源建模研究取得了重大进展，例如底物结合口袋的表征或在交替访问循环中作为铰链点的空间簇的识别。然而，一些基本问题，如囊泡氨基酸转运体的离子化学计量，仍未解决。
