Wnt-5a Modulates Recycling of Functional GABAA Receptors on Hippocampal NeuronsReportar como inadecuado




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Resumen

GABAA receptors GABAA-Rs play a significant role in mediating fast synaptic inhibition and it is the main inhibitory receptor in theCNS. The role of Wnt signaling in coordinating synapse structure and function in the mature CNS is poorly understood. In previousstudies we found that Wnt ligands can modulate excitatory synapses through remodeling both presynaptic and postsynaptic regions. Inthis current study we provide evidence for the effect of Wnt-5a on postsynaptic GABAA-Rs. We observed that Wnt-5a induces surfaceexpression and maintenance of this receptor in the neuronal membrane. The evoked IPSC recordings in rat hippocampal slice indicatethat Wnt-5a can regulates postsynaptically the hippocampal inhibitory synapses. We found also that Wnt-5a: a induces the insertionand clustering of GABAA-Rs in the membrane; b increases the amplitude of GABA-currents due exclusively to postsynaptic mechanisms;c does not affect the endocytic process, but increases the receptor recycling. Finally, all these effects on the GABAA-Rs aremediated by the activation of calcium-calmodulin-dependent kinase II CaMKII. Therefore, we postulate that Wnt-5a, by activation ofCaMKII, induces the recycling of functional GABAA-Rs on the mature hippocampal neurons.



Autor: Cuitino, Loreto; - Godoy, Juan A.; - Farías, Ginny G.; - Couve Correa, Andrés; - Bonansco, Christian; - Fuenzalida, Marco; - In

Fuente: http://repositorio.uchile.cl/



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