RGD Reference Report - Membrane-derived phospholipids control synaptic neurotransmission and plasticity. - Rat Genome Database

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Membrane-derived phospholipids control synaptic neurotransmission and plasticity.

Authors: García-Morales, Victoria  Montero, Fernando  González-Forero, David  Rodríguez-Bey, Guillermo  Gómez-Pérez, Laura  Medialdea-Wandossell, María Jesús  Domínguez-Vías, Germán  García-Verdugo, José Manuel  Moreno-López, Bernardo 
Citation: García-Morales V, etal., PLoS Biol. 2015 May 21;13(5):e1002153. doi: 10.1371/journal.pbio.1002153. eCollection 2015 May.
RGD ID: 155230734
Pubmed: PMID:25996636   (View Abstract at PubMed)
PMCID: PMC4440815   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pbio.1002153   (Journal Full-text)

Synaptic communication is a dynamic process that is key to the regulation of neuronal excitability and information processing in the brain. To date, however, the molecular signals controlling synaptic dynamics have been poorly understood. Membrane-derived bioactive phospholipids are potential candidates to control short-term tuning of synaptic signaling, a plastic event essential for information processing at both the cellular and neuronal network levels in the brain. Here, we showed that phospholipids affect excitatory and inhibitory neurotransmission by different degrees, loci, and mechanisms of action. Signaling triggered by lysophosphatidic acid (LPA) evoked rapid and reversible depression of excitatory and inhibitory postsynaptic currents. At excitatory synapses, LPA-induced depression depended on LPA1/Gαi/o-protein/phospholipase C/myosin light chain kinase cascade at the presynaptic site. LPA increased myosin light chain phosphorylation, which is known to trigger actomyosin contraction, and reduced the number of synaptic vesicles docked to active zones 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 of GABAergic transmission was correlated with an endocytosis-independent reduction of GABAA receptors, possibly by GABAAγ2 dephosphorylation and subsequent increased lateral diffusion. Furthermore, endogenous LPA signaling, mainly via LPA1, mediated activity-dependent inhibitory depression in a model of experimental synaptic plasticity. Finally, LPA signaling, most likely restraining the excitatory drive incoming to motoneurons, regulated performance of motor output commands, a basic brain processing task. We propose that lysophospholipids serve as potential local messengers that tune synaptic strength to precedent activity of the neuron.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Lpar1RatGABA-ergic synapse is_active_inEXP PMID:25996636SynGO 
Lpar1RatGABA-ergic synapse is_active_inIDA PMID:25996636SynGO 
Lpar1RatGABA-ergic synapse is_active_inIEP PMID:25996636SynGO 
Lpar1RatGABA-ergic synapse is_active_inIMP PMID:25996636SynGO 
Lpar1Ratglutamatergic synapse is_active_inEXP PMID:25996636SynGO 
Lpar1Ratglutamatergic synapse is_active_inIDA PMID:25996636SynGO 
Lpar1Ratglutamatergic synapse is_active_inIEP PMID:25996636SynGO 
Lpar1Ratglutamatergic synapse is_active_inIMP PMID:25996636SynGO 
Lpar1Ratpostsynaptic membrane is_active_inIDA PMID:25996636SynGO 
Lpar1Ratpresynaptic membrane is_active_inIDA PMID:25996636SynGO 

Objects Annotated

Genes (Rattus norvegicus)
Lpar1  (lysophosphatidic acid receptor 1)


Additional Information