Wnt-5a Modulates Recycling of Functional GABAA Receptors on Hippocampal Neurons
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2010-06-23Metadata
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Cuitino, Loreto
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Wnt-5a Modulates Recycling of Functional GABAA Receptors on Hippocampal Neurons
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Abstract
GABAA receptors (GABAA-Rs) play a significant role in mediating fast synaptic inhibition and it is the main inhibitory receptor in the
CNS. The role of Wnt signaling in coordinating synapse structure and function in the mature CNS is poorly understood. In previous
studies we found that Wnt ligands can modulate excitatory synapses through remodeling both presynaptic and postsynaptic regions. In
this current study we provide evidence for the effect of Wnt-5a on postsynaptic GABAA-Rs. We observed that Wnt-5a induces surface
expression and maintenance of this receptor in the neuronal membrane. The evoked IPSC recordings in rat hippocampal slice indicate
that Wnt-5a can regulates postsynaptically the hippocampal inhibitory synapses. We found also that Wnt-5a: (a) induces the insertion
and 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 are
mediated by the activation of calcium/calmodulin-dependent kinase II (CaMKII). Therefore, we postulate that Wnt-5a, by activation of
CaMKII, induces the recycling of functional GABAA-Rs on the mature hippocampal neurons.
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FONDECYT N°1071001
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URI: https://repositorio.uchile.cl/handle/2250/129084
DOI: DOI:10.1523/JNEUROSCI.5736-09.2010
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The Journal of Neuroscience, June 23, 2010 • 30(25):8411– 8420 • 8411
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