Guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin signaling at the developing neuromuscular junction

Earl W. Godfrey, Matthew Longacher, Hannah Neiswender, Russell C. Schwarte, Darren D Browning

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

During formation of the neuromuscular junction (NMJ), agrin secreted by motor axons signals the embryonic muscle cells to organize a postsynaptic apparatus including a dense aggregate of acetylcholine receptors (AChRs). Agrin signaling at the embryonic NMJ requires the activity of nitric oxide synthase (NOS). Common downstream effectors of NOS are guanylate cyclase (GC), which synthesizes cyclic GMP, and cyclic GMP-dependent protein kinase (PKG). Here we show that GC and PKG are important for agrin signaling at the embryonic NMJ of the frog, Xenopus laevis. Inhibitors of both GC and PKG reduced endogenous AChR aggregation in embryonic muscles by 50-85%, and blocked agrin-induced AChR aggregation in cultured embryonic muscle cells. A cyclic GMP analog, 8-bromo-cyclic GMP, increased endogenous AChR aggregation in embryonic muscles to 3- to 4-fold control levels. Overexpression of either GC or PKG in embryos increased AChR aggregate area by 60-170%, whereas expression of a dominant negative form of GC inhibited endogenous aggregation by 50%. These results indicate that agrin signaling in embryonic muscle cells requires the activity of GC and PKG as well as NOS.

Original languageEnglish (US)
Pages (from-to)195-201
Number of pages7
JournalDevelopmental Biology
Volume307
Issue number2
DOIs
StatePublished - Jul 15 2007

Fingerprint

Agrin
Cyclic GMP-Dependent Protein Kinases
Neuromuscular Junction
Guanylate Cyclase
Cholinergic Receptors
Receptor Aggregation
Myoblasts
Nitric Oxide Synthase
Cyclic GMP
Muscles
Xenopus laevis
Anura
Axons
Embryonic Structures

Keywords

  • Acetylcholine receptors
  • Agrin
  • Cyclic GMP
  • Cyclic GMP-dependent protein kinase
  • Guanylate cyclase
  • Muscle cells
  • Neuromuscular junction
  • Nitric oxide
  • Synapse formation
  • Xenopus embryos

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

Cite this

Guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin signaling at the developing neuromuscular junction. / Godfrey, Earl W.; Longacher, Matthew; Neiswender, Hannah; Schwarte, Russell C.; Browning, Darren D.

In: Developmental Biology, Vol. 307, No. 2, 15.07.2007, p. 195-201.

Research output: Contribution to journalArticle

Godfrey, Earl W. ; Longacher, Matthew ; Neiswender, Hannah ; Schwarte, Russell C. ; Browning, Darren D. / Guanylate cyclase and cyclic GMP-dependent protein kinase regulate agrin signaling at the developing neuromuscular junction. In: Developmental Biology. 2007 ; Vol. 307, No. 2. pp. 195-201.
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