title: Akt activation is necessary for growth factor-induced trafficking of functional K(Ca) channels in developing parasympathetic neurons.
abstract: The protein kinase Akt is a crucial regulator of neuronal survival and apoptosis. Here we show that Akt activation is necessary for mobilization of large-conductance K(Ca) channels in ciliary ganglion (CG) neurons evoked by beta-neuregulin-1 (NRG1) and transforming growth factor-beta1 (TGFbeta1). Application of NRG1 to embryonic day 9 (E9) CG neurons increased Akt phosphorylation, as observed previously for TGF(beta)1. NRG1- and TGF(beta)1-evoked stimulation of K(Ca) is blocked by inhibitors of PI3K by overexpression of a dominant-negative form of Akt, by overexpression of CTMP, an endogenous negative regulator of Akt, and by application of the Akt inhibitor 1L-6-hydroxymethyl-chiro-inositol 2-(R)-2-O-methyl-3-O-octadecylcarbonate (HIMO). Conversely, overexpression of a constitutively-active form of Akt was sufficient by itself to increase mobilization of functional K(Ca) channels. NRG1 and TGF(beta)1 evoked an Akt-dependent increase in cell-surface SLO alpha-subunits. These procedures have no effect on voltage-activated Ca2+ currents. Thus Akt plays an essential role in the developmental regulation of excitability in CG neurons.
authors.affiliation: Deptartment of Biology and Biochemistry, University of Houston, Houston, TX 77204-5513, USA.
authors.forename: Kwon-Seok
authors.initials: KS
authors.lastname: Chae
authors.forename: Miguel
authors.initials: M
authors.lastname: Martin-Caraballo
authors.forename: Marc
authors.initials: M
authors.lastname: Anderson
authors.forename: Stuart E
authors.initials: SE
authors.lastname: Dryer
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002478:Cells, Cultured; D002642:Chick Embryo; D003078:Colchicine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005726:Ganglia, Parasympathetic / Q000166:cytology* / Q000196:embryology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006133:Growth Substances / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects; D020890:Neuregulin-1 / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D015739:Nocodazole / Q000494:pharmacology; D018408:Patch-Clamp Techniques / Q000379:methods; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D013997:Time Factors; D014162:Transfection / Q000379:methods; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D053773:Transforming Growth Factor beta1
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D004791:Enzyme Inhibitors; D006133:Growth Substances; D020890:Neuregulin-1; D024681:Potassium Channels, Calcium-Activated; D011518:Proto-Oncogene Proteins; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D049452:Green Fluorescent Proteins; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D015739:Nocodazole; D003078:Colchicine