Wnt-5a Modulates Recycling of Functional GABAA Receptors on Hippocampal Neurons

被引:103
作者
Cuitino, Loreto
Godoy, Juan A.
Farias, Ginny G.
Couve, Andres [2 ]
Bonansco, Christian [3 ]
Fuenzalida, Marco [3 ]
Inestrosa, Nibaldo C. [1 ]
机构
[1] Pontificia Univ Catolica Chile, Fac Ciencias Biol, Ctr Regulac Celular & Patol Joaquin V Luco,CARE, Dept Biol Celular & Mol,Inst Milenio,Ctr Envejeci, Santiago 8331010, Chile
[2] Univ Chile, Fac Med, Inst Ciencias Biomed, Santiago 8380453, Chile
[3] Univ Valparaiso, Fac Ciencias, Dept Fisiol, Ctr Neurobiol & Plasticidad Desarrollo, Valparaiso 2360102, Chile
关键词
GAMMA-AMINOBUTYRIC-ACID; SYNAPTIC-TRANSMISSION; SIGNALING PATHWAY; INCREASED NUMBER; TRAFFICKING; POTENTIATION; ENDOCYTOSIS; SUBUNIT; INHIBITION; CURRENTS;
D O I
10.1523/JNEUROSCI.5736-09.2010
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
GABA(A) receptors (GABA(A)-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 GABA(A)-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 GABA(A)-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 GABA(A)-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 GABA(A)-Rs on the mature hippocampal neurons.
引用
收藏
页码:8411 / 8420
页数:10
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