Ras-dependent and Ras-independent effects of PI3K in Drosophila motor neurons.
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.
Department of Biochemistry and Cell Biology, Rice University, Houston, TX 77005, USA.
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Johnson
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Chun-Jen Lin
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Stern
D000818:Animals; D001665:Binding Sites; D058534:Class I Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology / Q000378:metabolism; D004789:Enzyme Activation; D009046:Motor Neurons / Q000166:cytology / Q000201:enzymology / Q000378:metabolism* / Q000502:physiology; D009154:Mutation; D017729:Presynaptic Terminals / Q000648:ultrastructure; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D055366:Synaptic Potentials; D019076:Transgenes; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D021122:Protein Subunits; D018094:Receptors, Metabotropic Glutamate; C494781:mGluR protein, Drosophila; D058534:Class I Phosphatidylinositol 3-Kinases; D018631:ras Proteins