The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity.
The small GTPase Arf1 modulates Arp2/3-mediated actin polymerization via PICK1 to regulate synaptic plasticity.
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DOI：
10.1016/j.neuron.2013.05.003
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发表时间：
2013-07-24
期刊：
影响因子：
16.2
通讯作者：
Hanley JG
中科院分区：
文献类型：
--
作者：
Rocca DL;Amici M;Antoniou A;Blanco Suarez E;Halemani N;Murk K;McGarvey J;Jaafari N;Mellor JR;Collingridge GL;Hanley JG
PICK1抑制Arp2/3介导的肌动蛋白聚合是AMPA受体(AMPAR)内化和长期抑制(LTD)的核心机制，但NMDAR激活时调节这一过程的信号通路尚不清楚。在这里，我们定义了GTPase Arf1在这个过程中的功能。我们发现Arf1-GTP与PICK1结合以限制PICK1对Arp2/3活性的抑制。表达不与PICK1结合的突变体Arf1会导致海马神经元中含有GluA2的AMPAR表面水平降低，并导致海马神经元中较小的棘突，从而阻止NMDA诱导的AMPAR内化和脊柱收缩。在器官切片中，在表达突变Arf1的神经元中，AMPAR兴奋性突触后电流的NMDAR依赖的LTD被完全取消。此外，NMDAR刺激通过Arf-GAP GIT1下调Arf1的激活和与PICK1的结合。本研究将Arf1定义为通过调节PICK1来调节肌动蛋白动力学和突触功能的关键调节因子。Arf1-PICK1-Arp2/3途径调节肌动蛋白聚合NMDAR激活激活Arf-GAP GIT1使Arf1失活Arf1控制NMDAR依赖的、PICK1介导的AMPAR运输和LTD Arf1在囊泡运输中扮演非典型角色，不同于COPI对Rocca等人的调控。结果表明，Arf1通过调节PICK1介导的Arp2/3抑制来调节树突棘中的肌动蛋白动态。这控制了脊柱的大小、AMPAR的运输，从而控制了突触的传递。本研究将Arf1定义为通过PICK1调节肌动蛋白动力学和突触可塑性的关键调节因子。
Inhibition of Arp2/3-mediated actin polymerization by PICK1 is a central mechanism to AMPA receptor (AMPAR) internalization and long-term depression (LTD), although the signaling pathways that modulate this process in response to NMDA receptor (NMDAR) activation are unknown. Here, we define a function for the GTPase Arf1 in this process. We show that Arf1-GTP binds PICK1 to limit PICK1-mediated inhibition of Arp2/3 activity. Expression of mutant Arf1 that does not bind PICK1 leads to reduced surface levels of GluA2-containing AMPARs and smaller spines in hippocampal neurons, which occludes subsequent NMDA-induced AMPAR internalization and spine shrinkage. In organotypic slices, NMDAR-dependent LTD of AMPAR excitatory postsynaptic currents is abolished in neurons expressing mutant Arf1. Furthermore, NMDAR stimulation downregulates Arf1 activation and binding to PICK1 via the Arf-GAP GIT1. This study defines Arf1 as a critical regulator of actin dynamics and synaptic function via modulation of PICK1. The Arf1-PICK1-Arp2/3 pathway regulates actin polymerization NMDAR activation activates the Arf-GAP GIT1 to deactivate Arf1 Arf1 controls NMDAR-dependent, PICK1-mediated AMPAR trafficking and LTD A noncanonical role is described for Arf1 in vesicle traffic, distinct from COPI regulation Rocca et al. show that Arf1 regulates actin dynamics in dendritic spines by modulating PICK1-mediated Arp2/3 inhibition. This controls spine size, AMPAR trafficking, and hence synaptic transmission. This study defines Arf1 as a critical regulator of actin dynamics and synaptic plasticity via PICK1 modulation.
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DOI：
10.1523/jneurosci.1042-04.2004
发表时间：
2004-06-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
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通讯作者：
Henley JM
影响因子：
4.7
作者：
Palmer, MJ;Irving, AJ;Collingridge, GL
通讯作者：
Collingridge, GL
影响因子：
3
作者：
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通讯作者：
Collingridge, Graham L.
影响因子：
16.2
作者：
Lu, W;Ziff, EB
通讯作者：
Ziff, EB
DOI：
10.1083/jcb.200809046
发表时间：
2009-04-20
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hotulainen P;Llano O;Smirnov S;Tanhuanpää K;Faix J;Rivera C;Lappalainen P
通讯作者：
Lappalainen P