Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuron. 2003 Nov 13;40(4):703-17.

Implication of geranylgeranyltransferase I in synapse formation.

Author information

1
Department of Neurobiology, Civitan International Research Center, University of Alabama at Birmingham, Birmingham, AL 35294, USA.

Abstract

Agrin activates the transmembrane tyrosine kinase MuSK to mediate acetylcholine receptor (AChR) clustering at the neuromuscular junction (NMJ). However, the intracellular signaling mechanism downstream of MuSK is poorly characterized. This study provides evidence that geranylgeranyltransferase I (GGT) is an important signaling component in the Agrin/MuSK pathway. Agrin causes a rapid increase in tyrosine phosphorylation of the alpha(G/F) subunit of GGT and in GGT activity. Inhibition of GGT activity or expression prevents muscle cells from forming AChR clusters in response to Agrin and attenuates the formation of neuromuscular synapses in spinal neuron-muscle cocultures. Importantly, transgenic mice expressing an alpha(G/F) mutant demonstrate NMJ defects with wider endplate bands and smaller AChR plaques. These results support the notion that prenylation is necessary for AChR clustering and the NMJ formation and/or maintenance, revealing an active role of GGT in Agrin/MuSK signaling.

PMID:
14622576
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Elsevier Science
    Loading ...
    Support Center