TY - JOUR
T1 - Neurotransmitter receptor dynamics studied in vivo by reversible photo-unbinding of fluorescent ligands
AU - Akaaboune, Mohammed
AU - Grady, R. Mark
AU - Turney, Steve
AU - Sanes, Joshua R.
AU - Lichtman, Jeff W.
N1 - Funding Information:
This work was supported by NIH (J.W.L., R.M.G., and J.R.S.), NRSA (M.A.), the Muscular Dystrophy Association (J.W.L.), and the Bakewell NeuroImaging Fund. We thank the members of our laboratory for discussions and Drs. John M. Jean, Ann Marie Craig, Robert Wilkinson, and Nick Turro for helpful discussions about this work.
PY - 2002/6/13
Y1 - 2002/6/13
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0037071873&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(02)00739-0
DO - 10.1016/S0896-6273(02)00739-0
M3 - Article
C2 - 12086635
AN - SCOPUS:0037071873
SN - 0896-6273
VL - 34
SP - 865
EP - 876
JO - Neuron
JF - Neuron
IS - 6
ER -