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First published online 18 October 2006
doi: 10.1242/dev.02619

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: dev.02619v1 133/22/4485    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in Development Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Bruneau, E. G. Articles by Akaaboune, M. Search for Related Content PubMed PubMed Citation Articles by Bruneau, E. G. Articles by Akaaboune, M.

The dynamics of recycled acetylcholine receptors at the neuromuscular junction in vivo

Department of Molecular, Cellular and Developmental Biology and Neuroscience Program, University of Michigan, 830 North University Avenue, Ann Arbor, MI 48109, USA.

^* Author for correspondence (e-mail: makaabou{at}umich.edu)

Accepted 7 September 2006

At the peripheral neuromuscular junction (NMJ), a significant number of nicotinic acetylcholine receptors (AChRs) recycle back into the postsynaptic membrane after internalization to intermingle with not-yet-internalized `pre-existing' AChRs. However, the way in which these receptor pools are maintained and regulated at the NMJ in living animals remains unknown. Here, we demonstrate that recycled receptors in functional synapses are removed approximately four times faster than pre-existing receptors, and that most removed recycled receptors are replaced by new recycled ones. In denervated NMJs, the recycling of AChRs is significantly depressed and their removal rate increased, whereas direct muscle stimulation prevents their loss. Furthermore, we show that protein tyrosine phosphatase inhibitors cause the selective accumulation of recycled AChRs in the peri-synaptic membrane without affecting the pre-existing AChR pool. The inhibition of serine/threonine phosphatases, however, has no effect on AChR recycling. These data show that recycled receptors are remarkably dynamic, and suggest a potential role for tyrosine dephosphorylation in the insertion and maintenance of recycled AChRs at the postsynaptic membrane. These findings may provide insights into long-term recycling processes at less accessible synapses in the central nervous system in vivo.

Key words: Recycling, Receptor dynamics, Half-life, Phosphorylation, Synaptic activity

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