Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands

被引:88
作者
Akaaboune, M [1 ]
Grady, RM [1 ]
Turney, S [1 ]
Sanes, JR [1 ]
Lichtman, JW [1 ]
机构
[1] Washington Univ, Sch Med, Dept Anat & Neurobiol, St Louis, MO 63110 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0896-6273(02)00739-0
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:865 / 876
页数:12
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