Research article summary (published 17 May 2003):

A novel pathway for MuSK to induce key genes in neuromuscular synapse formation.

Full Abstract

At the developing neuromuscular junction the Agrin receptor MuSK is the central organizer of subsynaptic differentiation induced by Agrin from the nerve. The expression of musk itself is also regulated by the nerve, but the mechanisms involved are not known. Here, we analyzed the activation of a musk promoter reporter construct in muscle fibers in vivo and in cultured myotubes, using transfection of multiple combinations of expression vectors for potential signaling components. We show that neuronal Agrin by activating MuSK regulates the expression of musk via two pathways: the Agrin-induced assembly of muscle-derived neuregulin (NRG)-1/ErbB, the pathway thought to regulate acetylcholine receptor (AChR) expression at the synapse, and via a direct shunt involving Agrin-induced activation of Rac. Both pathways converge onto the same regulatory element in the musk promoter that is also thought to confer synapse-specific expression to AChR subunit genes. In this way, a positive feedback signaling loop is established that maintains musk expression at the synapse when impulse transmission becomes functional. The same pathways are used to regulate synaptic expression of AChR epsilon. We propose that the novel pathway stabilizes the synapse early in development, whereas the NRG/ErbB pathway supports maintenance of the mature synapse.

Author information

Author/s: Lacazette, Eric (E); Le Calvez, Sophie (S); Gajendran, Nadesan (N); Brenner, Hans Rudolf (HR);

Affiliation: Department of Physiology, University of Basel, CH-4056 Basel, Switzerland.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Journal of cell biology (J Cell Biol), published in United States. (Language: eng)

Reference: 2003-May; vol 161 (issue 4) : pp 727-36

Dates: Created 2003/05/28; Completed 2003/07/08; Revised 2008/11/21;

PMID: 12756238, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - metabolism Amino Acid Sequence Animals Cell Line Cloning, Molecular DNA-Binding Proteins - metabolism Enzyme Activation GA-Binding Protein Transcription Factor Gene Expression Regulation, Developmental Humans Mice

Molecular Sequence Data Muscle Fibers, Skeletal - metabolism Neuromuscular Junction - genetics; metabolism Promoter Regions, Genetic - genetics Rats Receptor Protein-Tyrosine Kinases - chemistry; genetics; metabolism Receptors, Cholinergic - chemistry; genetics; metabolism Sequence Homology, Amino Acid Signal Transduction Synapses - genetics; metabolism Transcription Factors - metabolism

Associated Chemicals: Agrin (0) ; DNA-Binding Proteins (0) ; GA-Binding Protein Transcription Factor (0) ; Receptors, Cholinergic (0) ; Transcription Factors (0) ; Receptor Protein-Tyrosine Kinases (EC 2.7.1.112) ; MUSK protein, human (EC 2.7.10.1)

Related articles

These are the highest related articles currently in the database:

• Neuregulin inhibits acetylcholine receptor aggregation in myotubes. 18 May 2004
• Mutations causing DOK7 congenital myasthenia ablate functional motifs in Dok-7. 27 Dec 2007
• Expression of Eph receptors in skeletal muscle and their localization at the neuromuscular junction. 30 May 2001
• Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. 30 Jul 2002
• Regulation of acetylcholine receptor clustering by the tumor suppressor APC. 19 Sep 2003
• Syne-1, a dystrophin- and Klarsicht-related protein associated with synaptic nuclei at the neuromuscular junction. 11 Oct 2000
• ATP acts via P2Y1 receptors to stimulate acetylcholinesterase and acetylcholine receptor expression: transduction and transcription control. 30 May 2003
• Defective neuromuscular synaptogenesis in mice expressing constitutively active ErbB2 in skeletal muscle fibers. 6 Nov 2005
• [The role of protein tyrosine phosphatases Shp-2 involved in the formation of the neuromuscular junction] 16 Apr 2006

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.