Irfan Muhammad, Zurawski Zack, Hamm Heidi E, Bark Christina, Stanton Patric K
Department of Molecular Medicine and Surgery, The Rolf Luft Research Centre for Diabetes and Endocrinology, Karolinska Institutet, Stockholm, Sweden.
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, New York, USA.
Neuroreport. 2019 Jul 3;30(10):695-699. doi: 10.1097/WNR.0000000000001258.
Three SNARE proteins, SNAP-25, syntaxin 1A, and VAMP2 or synaptobrevin 2, constitute the minimal functional machinery needed for the regulated secretion of neurotransmitters. Dynamic changes in the regulated release of neurotransmitters are associated with the induction of long-term plasticity at central synapses. In-vitro studies have validated the C-terminus of SNAP-25 as a target for inhibitory Gi/o-coupled G-protein coupled receptors at a number of synapses. The physiological consequences of the interaction between Gi/o proteins and SNAP-25 in the context of activity-dependent long-term synaptic plasticity are not well understood. Here, we report direct ex-vivo evidence of the involvement of the C-terminus of SNAP-25 in inducing long-term potentiation of synaptic strength at Schaffer collateral-CA1 synapses using a gene-targeted mouse model with truncated C-terminus (carboxyl terminus) of SNAP-25. It has been shown previously that truncation of the three extreme C-terminal residues in SNAP-25[INCREMENT]3 homozygote mice reduces its interaction with the inhibitory Gβγ subunits two-fold. In in-vitro hippocampal slices, we show that these SNAP-25[INCREMENT]3 mice express significantly larger magnitude of long-term potentiation at hippocampal Schaffer collateral-CA1 synapses.
三种SNARE蛋白，即SNAP-25、 syntaxin 1A和VAMP2（或突触小泡蛋白2），构成了神经递质调节性分泌所需的最小功能机制。神经递质调节性释放的动态变化与中枢突触长期可塑性的诱导有关。体外研究已证实，在许多突触中，SNAP-25的C末端是抑制性Gi/o偶联G蛋白偶联受体的作用靶点。在活动依赖的长期突触可塑性背景下，Gi/o蛋白与SNAP-25相互作用的生理后果尚未得到充分了解。在此，我们使用具有截短SNAP-25 C末端（羧基末端）的基因靶向小鼠模型，报告了SNAP-25 C末端参与诱导海马体Schaffer侧支-CA1突触处突触强度长期增强的直接离体证据。先前已表明，SNAP-25[INCREMENT]3纯合子小鼠中三个极端C末端残基的截短使其与抑制性Gβγ亚基的相互作用减少了两倍。在体外海马体切片中，我们发现这些SNAP-25[INCREMENT]3小鼠在海马体Schaffer侧支-CA1突触处表现出明显更大程度的长期增强。
