RT journal article
T1 Membrane-derived phospholipids control synaptic neurotransmission and plasticity
A1 García Morales, Victoria
A1 Montero, Fernando
A1 González Forero, David
A1 Rodríguez Bey, Guillermo
A1 Gómez Pérez, Laura
A1 Medialdea Wandossell, María Jesús
A1 Domínguez Vías, Germán
A1 García Verdugo, José Manuel
A1 Moreno López, Bernardo
A2 BiomedicinaBiotecnología y Salud Pública
K1 LPA
K1 motoneurona
K1 GABA
AB Synaptic communication is a dynamic process that is key to the regulation of neuronal excitabilityand information processing in the brain. To date, however, the molecular signals controllingsynaptic dynamics have been poorly understood. Membrane-derived bioactivephospholipids are potential candidates to control short-term tuning of synaptic signaling, aplastic event essential for information processing at both the cellular and neuronal networklevels in the brain. Here, we showed that phospholipids affect excitatory and inhibitory neurotransmissionby different degrees, loci, and mechanisms of action. Signaling triggeredby lysophosphatidic acid (LPA) evoked rapid and reversible depression of excitatory andinhibitory postsynaptic currents. At excitatory synapses, LPA-induced depression dependedon LPA1/Gαi/o-protein/phospholipase C/myosin light chain kinase cascade at thepresynaptic site. LPA increased myosin light chain phosphorylation, which is known to triggeractomyosin contraction, and reduced the number of synaptic vesicles docked to activezones in excitatory boutons. At inhibitory synapses, postsynaptic LPA signaling led to dephosphorylation,and internalization of the GABAAγ2 subunit through the LPA1/Gα12/13-protein/RhoA/Rho kinase/calcineurin pathway. However, LPA-induced depression ofGABAergic transmission was correlated with an endocytosis-independent reduction ofGABAA receptors, possibly by GABAAγ2 dephosphorylation and subsequent increased lateraldiffusion. Furthermore, endogenous LPA signaling, mainly via LPA1, mediated activitydependentinhibitory depression in a model of experimental synaptic plasticity. Finally, LPAsignaling, most likely restraining the excitatory drive incoming to motoneurons, regulatedperformance of motor output commands, a basic brain processing task. We propose thatlysophospholipids serve as potential local messengers that tune synaptic strength to precedentactivity of the neuron.
PB Public Library of Science
SN 1544-9173
YR 2015
FD 2015-09
LK http://hdl.handle.net/10498/30961
UL http://hdl.handle.net/10498/30961
LA eng
DS Repositorio Institucional de la Universidad de Cádiz
RD 21-sep-2026