QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, July 4, 2007, 27(27):7183-7195; doi:10.1523/JNEUROSCI.1609-07.2007

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science 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 ISI Web of Science (5) Citing Articles via Google Scholar Google Scholar Articles by Ksiazek, I. Articles by Ruegg, M. A. Search for Related Content PubMed PubMed Citation Articles by Ksiazek, I. Articles by Ruegg, M. A.

 Previous Article  |  Next Article 

Cellular/Molecular
Synapse Loss in Cortex of Agrin-Deficient Mice after Genetic Rescue of Perinatal Death

Iwona Ksiazek,¹ Constanze Burkhardt,¹ Shuo Lin,¹ Riad Seddik,² Marcin Maj,¹ Gabriela Bezakova,¹ Mathias Jucker,³ Silvia Arber,^1,4 Pico Caroni,⁴ Joshua R. Sanes,⁵ Bernhard Bettler,² and Markus A. Ruegg¹

¹Biozentrum and ²Institute of Physiology, Department of Clinical-Biological Sciences, University of Basel, CH-4056 Basel, Switzerland, ³Department of Cellular Neurology, Hertie-Institute of Clinical Brain Research, D-72076 Tübingen, Germany, ⁴Friedrich Miescher Institute, CH-4058 Basel, Switzerland, and ⁵Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 01238

Correspondence should be addressed to Dr. Markus A. Ruegg, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Email: markus-a.ruegg{at}unibas.ch

Agrin-deficient mice die at birth because of aberrant development of the neuromuscular junctions. Here, we examined the role of agrin at brain synapses. We show that agrin is associated with excitatory but not inhibitory synapses in the cerebral cortex. Most importantly, we examined the brains of agrin-deficient mice whose perinatal death was prevented by the selective expression of agrin in motor neurons. We find that the number of presynaptic and postsynaptic specializations is strongly reduced in the cortex of 5- to 7-week-old mice. Consistent with a reduction in the number of synapses, the frequency of miniature postsynaptic currents was greatly decreased. In accordance with the synaptic localization of agrin to excitatory synapses, changes in the frequency were only detected for excitatory but not inhibitory synapses. Moreover, we find that the muscle-specific receptor tyrosine kinase MuSK, which is known to be an essential component of agrin-induced signaling at the neuromuscular junction, is also localized to a subset of excitatory synapses. Finally, some components of the mitogen-activated protein (MAP) kinase pathway, which has been shown to be activated by agrin in cultured neurons, are deregulated in agrin-deficient mice. In summary, our results provide strong evidence that agrin plays an important role in the formation and/or the maintenance of excitatory synapses in the brain, and we provide evidence that this function involves MAP kinase signaling.

Key words: neuromuscular synapse; gene expression; excitatory synapse; MuSK; spines; MAP kinase

---

Received Sept. 1, 2006; revised May 25, 2007; accepted May 26, 2007.

Correspondence should be addressed to Dr. Markus A. Ruegg, Biozentrum, University of Basel, Klingelbergstrasse 70, CH-4056 Basel, Switzerland. Email: markus-a.ruegg{at}unibas.ch

This article has been cited by other articles:

				S. Lin, M. Maj, G. Bezakova, J. P. Magyar, H. R. Brenner, and M. A. Ruegg Muscle-wide secretion of a miniaturized form of neural agrin rescues focal neuromuscular innervation in agrin mutant mice PNAS, August 12, 2008; 105(32): 11406 - 11411. [Abstract] [Full Text] [PDF]

				A. Stephan, J. M. Mateos, S. V. Kozlov, P. Cinelli, A. D. Kistler, S. Hettwer, T. Rulicke, P. Streit, B. Kunz, and P. Sonderegger Neurotrypsin cleaves agrin locally at the synapse FASEB J, June 1, 2008; 22(6): 1861 - 1873. [Abstract] [Full Text] [PDF]

				S. Lin, L. Landmann, M. A. Ruegg, and H. R. Brenner The Role of Nerve- versus Muscle-Derived Factors in Mammalian Neuromuscular Junction Formation J. Neurosci., March 26, 2008; 28(13): 3333 - 3340. [Abstract] [Full Text] [PDF]

				R. Frischknecht, A. Fejtova, M. Viesti, A. Stephan, and P. Sonderegger Activity-Induced Synaptic Capture and Exocytosis of the Neuronal Serine Protease Neurotrypsin J. Neurosci., February 13, 2008; 28(7): 1568 - 1579. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help