Phosphoinositide 3-kinase mediated signaling in lobster olfactory receptor neurons.
In vertebrates and some invertebrates, odorant molecules bind to G protein-coupled receptors on olfactory receptor neurons (ORNs) to initiate signal transduction. Phosphoinositide 3-kinase (PI3K) activity has been implicated physiologically in olfactory signal transduction, suggesting a potential role for a G protein-coupled receptor-activated class I PI3K. Using isoform-specific antibodies, we identified a protein in the olfactory signal transduction compartment of lobster ORNs that is antigenically similar to mammalian PI3Kgamma and cloned a gene for a PI3K with amino acid homology with PI3Kbeta. The lobster olfactory PI3K co-immunoprecipitates with the G protein alpha and beta subunits, and an odorant-evoked increase in phosphatidylinositol (3,4,5)-trisphosphate can be detected in the signal transduction compartment of the ORNs. PI3Kgamma and beta isoform-specific inhibitors reduce the odorant-evoked output of lobster ORNs in vivo. Collectively, these findings provide evidence that PI3K is indeed activated by odorant receptors in lobster ORNs and further support the potential involvement of G protein activated PI3K signaling in olfactory transduction.
Corey
Elizabeth A
EA
Whitney Laboratory, Center for Smell and Taste, McKnight Brain Institute, University of Florida, Gainesville, Florida 32080-8610, USA. eacorey@whitney.ufl.edu
Bobkov
Yuriy
Y
Pezier
Adeline
A
Ache
Barry W
BW
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D047468:Immunoprecipitation / Q000379:methods; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009812:Odorants; D009830:Olfactory Bulb / Q000166:cytology*; D018034:Olfactory Receptor Neurons / Q000187:drug effects / Q000502:physiology*; D033521:Palinuridae / Q000033:anatomy & histology; D018408:Patch-Clamp Techniques / Q000379:methods; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D004791:Enzyme Inhibitors; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D019869:Phosphatidylinositol 3-Kinases