Implication of Geranylgeranyltransferase I in Synapse Formation
| Autor: | Zhen G Luo, Hyunsoo Shawn Je, Bai Lu, Feng Yang, Lin Mei, Zhi Hua Yang, Wen Cheng Xiong, G. Clem Dobbins, Qiang Wang |
|---|---|
| Jazyk: | angličtina |
| Předmět: |
rho GTP-Binding Proteins
Receptors Nicotinic chemistry.chemical_compound Mice Xenopus laevis 0302 clinical medicine Receptors Cholinergic Tyrosine Enzyme Inhibitors Phosphorylation Cells Cultured 0303 health sciences Agrin General Neuroscience musculoskeletal system Cell biology medicine.anatomical_structure Biochemistry Tyrosine kinase animal structures Neuroscience(all) Neuromuscular Junction Protein Prenylation Synaptic Membranes Mice Transgenic Biology digestive system Neuromuscular junction 03 medical and health sciences Organ Culture Techniques medicine Animals 030304 developmental biology Acetylcholine receptor Alkyl and Aryl Transferases Dose-Response Relationship Drug Receptor Protein-Tyrosine Kinases Tyrosine phosphorylation digestive system diseases Protein Subunits chemistry Animals Newborn nervous system Mutation Protein prenylation Peptides 030217 neurology & neurosurgery |
| Zdroj: | Neuron. (4):703-717 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/S0896-6273(03)00695-0 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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