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dc.contributor.advisor Stern, Michael
dc.creatorJohnson, Cassidy Brown
dc.date.accessioned 2013-03-08T00:34:48Z
dc.date.available 2013-03-08T00:34:48Z
dc.date.issued 2012
dc.identifier.citation Johnson, Cassidy Brown. "Ras-dependent and Ras-independent effects of PI3K in Drosophila motor neurons." (2012) Diss., Rice University. https://hdl.handle.net/1911/70281.
dc.identifier.urihttps://hdl.handle.net/1911/70281
dc.description.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 DmGIuRA. In contrast, the ability of PI3K to increase synaptic bouton number is Ras independent. These results suggest that distinct regulatory mechanisms underlie the effects of PI3K on distinct phenotypic outputs. We additionally found that the glutamate-activation of DmGIuRA initiates ERK signaling; however the signaling intermediates linking DmGIuRA to this kinase cascade are unknown.
dc.format.extent 151 p.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.subjectBiological sciences
Drosophila
Fragile X
Synaptic bouton number
Neuronal excitability
Metabotropic glutamate receptor
Autism
Ras
Neurosciences
Genetics
Cellular biology
dc.title Ras-dependent and Ras-independent effects of PI3K in Drosophila motor neurons
dc.identifier.digital JohnsonC
dc.type.genre Thesis
dc.type.material Text
thesis.degree.department Biochemistry and Cell Biology
thesis.degree.discipline Natural Sciences
thesis.degree.grantor Rice University
thesis.degree.level Doctoral
thesis.degree.name Doctor of Philosophy


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