HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 15, 10347-10354, April 14, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/15/10347    most recent M507502200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend 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 Krejci, E. Articles by Akaaboune, M. Search for Related Content PubMed PubMed Citation Articles by Krejci, E. Articles by Akaaboune, M. Social Bookmarking                      What's this?

Acetylcholinesterase Dynamics at the Neuromuscular Junction of Live Animals^*

Eric Krejci, Isabel Martinez-Pena y Valenzuela, Rafiqa Ameziane, and Mohammed Akaaboune¹

From the Department of Molecular, Cellular, and Developmental Biology and Neuroscience Program, University of Michigan, Ann Arbor, Michigan 48109 and INSERM U686, Biologie des Jonctions Neuromusculaires, 45 Rue des Saints Pères, 75006 Paris, France

At cholinergic synapses, acetylcholinesterase (AChE) is critical for ensuring normal synaptic transmission. However, little is known about how this enzyme is maintained and regulated in vivo. In this work, we demonstrate that the dissociation of fluorescently-tagged fasciculin 2 (a specific and selective peptide inhibitor of AChE) from AChE is extremely slow. This fluorescent probe was used to study the removal and insertion of AChE at individual synapses of living adult mice. After a one-time blockade of AChEs with fluorescent fasciculin 2, AChEs are removed from synapses initially at a faster rate (t_1/2 of 3 days) and later at a slower rate (t_1/2 of 12 days). Most of the removed AChEs are replaced by newly inserted AChEs over time. However, when AChEs are continuously blocked with fasciculin 2, the removal rate increases substantially (t_1/2 of 12 h), and most of the lost AChEs are not replaced by newly inserted AChE. Furthermore, complete one-time inactivation of AChE activity significantly increases the removal of postsynaptic nicotinic acetylcholine receptors (AChRs). Finally, time lapse imaging reveals that synaptic AChEs and AChRs that are removed from synapses are co-localized in the same pool after being internalized. These results demonstrate a remarkable AChE dynamism and argue for a potential link between AChE function and postsynaptic receptor lifetime.

Received for publication, July 11, 2005 , and in revised form, February 1, 2006.

^* This work was supported by the University of Michigan, NINDS, National Institutes of Health, Grant NS047332 (to M. A.), and CNRS, AFM, and la Fondation pour la Recherche Médicale (to E. K.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Molecular, Cellular and Developmental Biology, University of Michigan, 830 N. University Ave., Ann Arbor, MI 48109. Tel.: 734-647-8512; Fax: 734-647-0884; E-mail: makaabou{at}umich.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				I. Martinez-Pena y Valenzuela and M. Akaaboune Acetylcholinesterase Mobility and Stability at the Neuromuscular Junction of Living Mice Mol. Biol. Cell, August 1, 2007; 18(8): 2904 - 2911. [Abstract] [Full Text] [PDF]