title: Rap1 signaling prevents L-type calcium channel-dependent neurotransmitter release.
abstract: The small GTPase Rap1 contributes to fear learning and cortico-amygdala plasticity by inhibiting glutamate release from cortical neurons, but mechanisms of this inhibition remain unknown. Conversely, L-type calcium channels (LTCCs) become involved in glutamate release after fear learning and LTP induction. Here, we show that Rap1 deletion in mouse primary cortical neurons increases synaptic vesicle exocytosis without altering endocytosis or vesicle pool size in an LTCC-dependent manner. We identify Erk1/2 as the downstream effector of Rap1 and show that its inhibition increases plasma membrane expression of LTCCs near presynaptic terminals. We propose that the Rap1 signaling enables plasticity and fear learning by regulating LTCCs at cortico-amygdala synapses.
authors.affiliation: Unit on Behavioral Genetics, Laboratory of Molecular Pathophysiology, National Institute of Mental Health and Microscopy and Imaging Core, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland 20892, USA. jaichandar@gmail.com
authors.forename: Jaichandar
authors.initials: J
authors.lastname: Subramanian
authors.forename: Louis
authors.initials: L
authors.lastname: Dye
authors.forename: Alexei
authors.initials: A
authors.lastname: Morozov
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D002478:Cells, Cultured; D005089:Exocytosis / Q000502:physiology*; D005260:Female; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D020827:rap1 GTP-Binding Proteins / Q000172:deficiency* / Q000235:genetics
chemical_list: D020746:Calcium Channels, L-Type; D018377:Neurotransmitter Agents; D020827:rap1 GTP-Binding Proteins