Research article summary (published 30 Jan 2004):

Agrin-induced AChR aggregate formation requires cGMP and aggregate maturation requires activation of cGMP-dependent protein kinase.

Full Abstract

Previously, it was demonstrated that agrin acting through the gaseous, signaling molecule, nitric oxide (NO), induces the formation of AChR aggregates on myotubes in culture. Soluble guanylyl cyclase (sGC), which is present at the neuromuscular junction, is a common target of NO. Therefore, we hypothesized that sGC and cGMP are involved in the agrin signaling cascade. Inhibition of sGC hindered AChR aggregation in both agrin- and NO donor-treated cultured myotubes; whereas, a cGMP analogue was able to induce the formation of AChR aggregates on naïve muscle cells. Due to the presence of cyclic GMP-dependent protein kinase (PKG) at the neuromuscular junction, we tested the ability of a PKG inhibitor to alter the agrin signaling cascade. PKG inhibition did not prevent nascent AChR aggregate formation; however, these aggregates were diffuse and composed of numerous microaggregates consistent with incomplete maturation. Thus, we conclude that cGMP is important for the initiation of AChR aggregation, while PKG is involved in the maturation of AChR aggregates.

Author information

Author/s: Jones, Melissa A (MA); Werle, Michael J (MJ);

Affiliation: Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Grants: NS33320 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, U.S. Gov't, P.H.S.

Journal: Molecular and cellular neurosciences (Mol Cell Neurosci), published in United States. (Language: eng)

Reference: 2004-Feb; vol 25 (issue 2) : pp 195-204

Dates: Created 2004/03/15; Completed 2004/06/15; Revised 2007/11/14;

PMID: 15019937, 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.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Agrin - metabolism; pharmacology Animals Cell Differentiation - physiology Cells, Cultured Chick Embryo Cyclic GMP - analogs & derivatives; metabolism; pharmacology Cyclic GMP-Dependent Protein Kinases - antagonists & inhibitors; metabolism Dose-Response Relationship, Drug Enzyme Inhibitors - pharmacology

Guanylate Cyclase Muscle, Skeletal - innervation Neuromuscular Junction - drug effects; embryology; enzymology Nitric Oxide - metabolism Nitric Oxide Donors - pharmacology Receptor Aggregation - drug effects; physiology Receptors, Cholinergic - drug effects; metabolism Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; metabolism Signal Transduction - physiology

Associated Chemicals: Agrin (0) ; Enzyme Inhibitors (0) ; Nitric Oxide Donors (0) ; Receptors, Cholinergic (0) ; Receptors, Cytoplasmic and Nuclear (0) ; Nitric Oxide (10102-43-9) ; 8-bromocyclic GMP (31356-94-2) ; Cyclic GMP (7665-99-8) ; Cyclic GMP-Dependent Protein Kinases (EC 2.7.1.37) ; Guanylate Cyclase (EC 4.6.1.2) ; soluble guanylyl cyclase (EC 4.6.1.2)

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