RRC ID 21906
Author Johnson C, Chun-Jen Lin C, Stern M.
Title Ras-dependent and Ras-independent effects of PI3K in Drosophila motor neurons.
Journal Genes Brain Behav
Abstract The lipid kinase PI3K plays key roles in cellular responses to activation of receptor tyrosine kinases or G protein coupled receptors such as the metabotropic glutamate receptor (mGluR). Activation of the PI3K catalytic subunit p110 occurs when the PI3K regulatory subunit p85 binds to phosphotyrosine residues present in upstream activating proteins. In addition, Ras is uniquely capable of activating PI3K in a p85-independent manner by binding to p110 at amino acids distinct from those recognized by p85. Because Ras, like p85, is activated by phosphotyrosines in upstream activators, it can be difficult to determine if particular PI3K-dependent processes require p85 or Ras. Here, we ask if PI3K requires Ras activity for either of two different PI3K-regulated processes within Drosophila larval motor neurons. To address this question, we determined the effects on each process of transgenes and chromosomal mutations that decrease Ras activity, or mutations that eliminate the ability of PI3K to respond to activated Ras. We found that PI3K requires Ras activity to decrease motor neuron excitability, an effect mediated by ligand activation of the single Drosophila mGluR DmGluRA. In contrast, the ability of PI3K to increase nerve terminal growth is Ras-independent. These results suggest that distinct regulatory mechanisms underlie the effects of PI3K on distinct phenotypic outputs.
Volume 11(7)
Pages 848-58
Published 2012-10-1
DOI 10.1111/j.1601-183X.2012.00822.x
PMID 22783951
MeSH Animals Binding Sites Class I Phosphatidylinositol 3-Kinases / genetics Class I Phosphatidylinositol 3-Kinases / metabolism* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Drosophila melanogaster / enzymology Drosophila melanogaster / metabolism Enzyme Activation Motor Neurons / cytology Motor Neurons / enzymology Motor Neurons / metabolism* Motor Neurons / physiology Mutation Presynaptic Terminals / ultrastructure Protein Subunits / genetics Protein Subunits / metabolism Receptors, Metabotropic Glutamate / genetics Receptors, Metabotropic Glutamate / metabolism Synaptic Potentials Transgenes ras Proteins / genetics ras Proteins / metabolism*
IF 3.397
Times Cited 2
Drosophila 1799R-2 1799R-3