Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands
Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands
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DOI：
10.1016/s0896-6273(02)00739-0
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发表时间：
2002-06-13
期刊：
影响因子：
16.2
通讯作者：
Lichtman, JW
中科院分区：
文献类型：
--
作者：
Akaaboune, M;Grady, RM;Lichtman, JW
我们发现，荧光标记的配体与其目标具有高亲和力，可以通过聚焦激光激发可逆地结合。通过连续的解结合和用不同颜色的α-银环蛇毒素重新标记，我们选择性地标记成年小鼠神经肌肉接头处的乙酰胆碱受体（AChRs）的相邻池。在体内的时间推移成像显示，突触AChRs完全混合在类似4天，许多突触外AChRs被纳入突触的每一天。在缺乏α-肌养短缩蛋白（肌养蛋白-糖蛋白复合物的一种成分）的小鼠中，乙酰胆碱受体转换率和混合率增加了4 - 5倍。这些结果表明显着的分子动力学基础的突触后膜的宏观稳定性，并建立α-dystrobrevin作为一个关键的控制点，调节流动性和营业额。
We show that fluorescently tagged ligands with high affinity for their targets can be reversibly unbound by focused laser excitation. By sequential unbinding and relabeling with different colors of alpha-bungarotoxin, we selectively labeled adjacent pools of acetylcholine receptors [AChRs) at neuromuscular junctions of adult mice. Timelapse imaging in vivo revealed that synaptic AChRs completely intermingle over similar to4 days and many extrasynaptic AChRs are incorporated into the synapse each day. In mice that lacked alpha-dystrobrevin, a component of the dystrophin-glycoprotein complex, rates of AChR turnover, and intermingling were increased similar to4- to 5-fold. These results demonstrate remarkable molecular dynamism underlying macroscopic stability of the postsynaptic membrane, and establish alpha-dystrobrevin as a key control point for regulation of mobility and turnover.