Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity.
Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity.
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DOI：
10.1016/j.cell.2008.09.057
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发表时间：
2008-10-31
期刊：
影响因子：
64.5
通讯作者：
Ehlers, Michael D.
中科院分区：
文献类型：
--
作者：
Wang, Zhiping;Edwards, Jeffrey G.;Riley, Nathan;Provance, D. William, Jr.;Karcher, Ryan;Li, Xiang-dong;Davison, Ian G.;Ikebe, Mitsuo;Mercer, John A.;Kauer, Julie A.;Ehlers, Michael D.
哺乳动物大脑兴奋性突触的学习相关可塑性需要AMPA受体的运输和树突棘的生长。然而，耦合可塑性刺激的突触后货物的贩运机制知之甚少。在这里，我们证明了肌球蛋白Vb（MyoVb）是一种Ca 2+敏感性运动，在突触强度的长时程增强（LTP）过程中进行脊髓运输。在激活NMDA受体和相应的Ca 2+内流后，MyoVb与再循环内体（RE）相关联，触发内体的快速棘募集和棘中的局部胞吐作用。MyoVb或其与RE适配器Rab 11-FIP 2的相互作用的破坏废除了从RE的LTP诱导的胞吐作用，并防止AMPA受体插入和棘生长。此外，使用急性化学遗传策略诱导MyoVb与肌动蛋白的紧密结合根除海马切片中的LTP。因此，Ca 2+激活MyoVb捕获并动员RE用于AMPA受体插入和脊柱生长，提供了突触后可塑性的诱导和表达之间的机械联系。
Learning-related plasticity at excitatory synapses in the mammalian brain requires the trafficking of AMPA receptors and the growth of dendritic spines. However, the mechanisms that couple plasticity stimuli to the trafficking of postsynaptic cargo are poorly understood. Here we demonstrate that myosin Vb (MyoVb), a Ca2+-sensitive motor, conducts spine trafficking during long-term potentiation (LTP) of synaptic strength. Upon activation of NMDA receptors and corresponding Ca2+ influx, MyoVb associates with recycling endosomes (REs), triggering rapid spine recruitment of endosomes and local exocytosis in spines. Disruption of MyoVb or its interaction with the RE adaptor Rab11-FIP2 abolishes LTP-induced exocytosis from REs and prevents both AMPA receptor insertion and spine growth. Furthermore, induction of tight binding of MyoVb to actin using an acute chemical genetic strategy eradicates LTP in hippocampal slices. Thus, Ca2+-activated MyoVb captures and mobilizes of REs for AMPA receptor insertion and spine growth, providing a mechanistic link between the induction and expression of postsynaptic plasticity.
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