Integrin α3β1 suppresses long-term potentiation at inhibitory synapses on the cerebellar Purkinje neuron

Integrin α3β1 suppresses long-term potentiation at inhibitory synapses on the cerebellar Purkinje neuron
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DOI:
10.1016/j.mcn.2005.10.012
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发表时间:
2006-03-01
影响因子:
3.5
通讯作者:
Hirano, T
Hirano, T
中科院分区:
医学3区
文献类型:
--
作者:
Kawaguchi, SY;Hirano, T

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在小脑中抑制性中间神经元和浦肯野神经元(PN)之间的GABA能突触处,突触后去极化诱导GABA(A)受体反应性的长时程增强(称为反弹增强; RP)。在这里,我们表明,整合素,一种类型的细胞粘附分子,参与RP的调节。Mn ~(2+)激活整合素可抑制RP诱导的PN中GABA反应性和mIPSC,而针对整合素α 3或β 1亚基的功能阻断抗体可阻断该效应,但针对整合素α 5或α V亚基的功能阻断抗体则不能阻断该效应。此外,PN中整合素α 3亚基的过度表达本身就损害了RP的诱导。我们还表明,Src家族的蛋白酪氨酸激酶介导的整合素活性的RP诱导的抑制作用。因此,整合素/Src途径负调控诱导的长期可塑性在抑制性突触小脑PN。(c)2005年爱思唯尔公司All rights reserved.
At the GABAergic synapses between inhibitory interneurons and a Purkinje neuron (PN) in the cerebellum, the postsynaptic depolarization induces the long-term potentiation (called rebound potentiation; RP) of GABA(A) receptor responsiveness. Here, we show that integrins, a type of cell-adhesion molecules, are involved in the regulation of RP. Integrin activation by Mn2+ impaired the RP induction of GABA responsiveness and mIPSCs in PNs, which was abolished by the function blocking antibody against either integrin alpha 3 or beta 1 subunit, but not by that against alpha 5 or alpha V subunit. Furthermore, overexpression of integrin alpha 3 subunit in a PN by itself impaired the RP induction. We also show that Src-family of protein tyrosine kinases mediated the suppressive effect of integrin activity on the RP induction. Thus, the integrin/Src pathway negatively regulates the induction of long-term plasticity at inhibitory synapses on a cerebellar PN. (c) 2005 Elsevier Inc. All rights reserved.