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Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane

Schmidt, N. and Basu, S. and Sladecek, S. and Gatti, S. and van Haren, J. and Treves, S. and Pielage, J. and Galjart, N. and Brenner, H. R.. (2012) Agrin regulates CLASP2-mediated capture of microtubules at the neuromuscular junction synaptic membrane. Journal of Cell Biology, 198 (3). pp. 421-437.

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Official URL: http://edoc.unibas.ch/dok/A6174397

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Abstract

Agrin is the major factor mediating the neuronal regulation of postsynaptic structures at the vertebrate neuromuscular junction, but the details of how it orchestrates this unique three-dimensional structure remain unknown. Here, we show that agrin induces the formation of the dense network of microtubules in the subsynaptic cytoplasm and that this, in turn, regulates acetylcholine receptor insertion into the postsynaptic membrane. Agrin acted in part by locally activating phosphatidylinositol 3-kinase and inactivating GSK3beta, which led to the local capturing of dynamic microtubules at agrin-induced acetylcholine receptor (AChR) clusters, mediated to a large extent by the microtubule plus-end tracking proteins CLASP2 and CLIP-170. Indeed, in the absence of CLASP2, microtubule plus ends at the subsynaptic muscle membrane, the density of synaptic AChRs, the size of AChR clusters, and the numbers of subsynaptic muscle nuclei with their selective gene expression programs were all reduced. Thus, the cascade linking agrin to CLASP2-mediated microtubule capturing at the synaptic membrane is essential for the maintenance of a normal neuromuscular phenotype.
Faculties and Departments:03 Faculty of Medicine > Departement Biomedizin
03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Perioperative Patient Safety (Girard/Treves)
UniBasel Contributors:Brenner, Hans-Rudolf and Treves, Susan
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Rockefeller University Press
ISSN:0021-9525
e-ISSN:1540-8140
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:11 May 2017 09:17
Deposited On:25 Oct 2013 08:33

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