Data/hora: 12/06/2024 15:21:26

Provedor de dados: 	17	
País: 	United Kingdom	
Título: 	A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability	
Autores: 	Eric Howlett; Curtis C. J. Lin; William Lavery; Michael Stern.	
Data: 	2008-04-04	
Ano: 	2008	
Palavras-chave: 	Molecular Cell Biology; Neuroscience.	
Resumo: 	Negative feedback can act as a homeostatic mechanism to maintain neuronal activity at a particular specified value. At the Drosophila neuromuscular junction, a mutation in the type II metabotropic glutamate receptor gene (mGluRA) increased motor neuron excitability by disrupting an autocrine, glutamate-mediated negative feedback. We show that mGluRA mutations increase neuronal excitability by preventing PI3 kinase (PI3K) activation and consequently hyperactivating the transcription factor Foxo. Furthermore, glutamate application increases levels of phospho-Akt, a product of PI3K signaling, within motor nerve terminals in an mGluRA-dependent manner. In humans, PI3K and type II mGluRs are implicated in epilepsy, neurofibromatosis, autism, schizophrenia and other neurological disorders; however, neither the link between type II mGluRs and PI3K, nor the role of Foxo in the control of neuronal excitability, had been previously reported. Our work suggests that some of the deficits in these neurological disorders might result from disruption of glutamate-mediated homeostasis of neuronal excitability.	
Tipo: 	Manuscript	
Identificador: 	http://precedings.nature.com/documents/1767/version/1

oai:nature.com:10101/npre.2008.1767.1

http://hdl.handle.net/10101/npre.2008.1767.1	
Fonte: 	Nature Precedings	
Fonte: 	Creative Commons Attribution 3.0 License