7 votes

A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability

Eric Howlett¹, Curtis C. J. Lin¹, William Lavery¹ & Michael Stern¹

Correspondence: (Login to view email address)

1. Rice University, Department of Biochemistry and Cell biology

PDF (3.2 MB)

Document Type:

Manuscript

Date:

Received 04 April 2008 21:41 UTC; Posted 07 April 2008

Subjects:

Molecular Cell Biology, Neuroscience

Tags:

• synaptic transmission
• G-protein coupled receptors
• autism
• glutamate
• Epilepsy

Abstract:

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.

Discussion

Votes:

7 votes

(Login to vote)

Comments:

0 comments

(Login to post a comment)

Share:

(Login to share with a colleague)

Additional information

License:

This document is licensed to the public under the Creative Commons Attribution 3.0 License

How to cite this document:

Howlett, Eric, Lin, Curtis, Lavery, William, and Stern, Michael. A PI3K-mediated negative feedback regulates Drosophila motor neuron excitability. Available from Nature Precedings <http://hdl.handle.net/10101/npre.2008.1767.1> (2008)

Version info:

Other versions of this document in Nature Precedings

None.

Other versions of this document elsewhere on the web

None known.

Submit a new version link