title: Non-hyperpolarizing GABAB receptor activation regulates neuronal migration and neurite growth and specification by cAMP/LKB1.
abstract: γ-Aminobutyric acid is the principal inhibitory neurotransmitter in adults, acting through ionotropic chloride-permeable GABAA receptors (GABAARs), and metabotropic GABABRs coupled to calcium or potassium channels, and cyclic AMP signalling. During early development, γ-aminobutyric acid is the main neurotransmitter and is not hyperpolarizing, as GABAAR activation is depolarizing while GABABRs lack coupling to potassium channels. Despite extensive knowledge on GABAARs as key factors in neuronal development, the role of GABABRs remains unclear. Here we address GABABR function during rat cortical development by in utero knockdown (short interfering RNA) of GABABR in pyramidal-neuron progenitors. GABABR short interfering RNA impairs neuronal migration and axon/dendrite morphological maturation by disrupting cyclic AMP signalling. Furthermore, GABABR activation reduces cyclic AMP-dependent phosphorylation of LKB1, a kinase involved in neuronal polarization, and rescues LKB1 overexpression-induced defects in cortical development. Thus, non-hyperpolarizing activation of GABABRs during development promotes neuronal migration and morphological maturation by cyclic AMP/LKB1 signalling.
authors: Department of Neuroscience and Brain Technologies, Istituto Italiano di Tecnologia, Via Morego, 30 Genoa 16163, Italy.
authors: Guillaume
authors: G
authors: Bony
authors: Joanna
authors: J
authors: Szczurkowska
authors: Ilaria
authors: I
authors: Tamagno
authors: Maya
authors: M
authors: Shelly
authors: Andrea
authors: A
authors: Contestabile
authors: Laura
authors: L
authors: Cancedda
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D000818:Animals; D000831:Animals, Newborn; D001369:Axons / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D015153:Blotting, Western; D002465:Cell Movement / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D066298:In Vitro Techniques; D008969:Molecular Sequence Data; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D021122:Protein Subunits / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D018080:Receptors, GABA-B / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013003:Somatosensory Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
chemical_list: D005971:Glutamates; D021122:Protein Subunits; D034741:RNA, Small Interfering; D018080:Receptors, GABA-B; D000242:Cyclic AMP; D017346:Protein Serine-Threonine Kinases; C488755:Stk11 protein, rat; D000091162:AMP-Activated Protein Kinase Kinases
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