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

Mohammed Akaaboune, R. Mark Grady, Steve Turney, Joshua R. Sanes, Jeff W. Lichtman

Research output: Contribution to journalArticle

85 Scopus citations

Abstract

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 α-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 ∼4 days and many extrasynaptic AChRs are incorporated into the synapse each day. In mice that lacked α-dystrobrevin, a component of the dystrophin-glycoprotein complex, rates of AChR turnover, and intermingling were increased ∼4- to 5-fold. These results demonstrate remarkable molecular dynamism underlying macroscopic stability of the postsynaptic membrane, and establish α-dystrobrevin as a key control point for regulation of mobility and turnover.

Original languageEnglish
Pages (from-to)865-876
Number of pages12
JournalNeuron
Volume34
Issue number6
DOIs
StatePublished - Jun 13 2002

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