Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons
Differential roles of Rap1 and Rap2 small GTPases in neurite retraction and synapse elimination in hippocampal spiny neurons
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DOI：
10.1111/j.1471-4159.2006.04195.x
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发表时间：
2007-01-01
影响因子：
4.7
通讯作者：
Pak, Daniel T. S.
中科院分区：
文献类型：
--
作者：
Fu, Zhanyan;Lee, Sang Hyoung;Pak, Daniel T. S.
小GTP酶的Rap家族涉及突触可塑性的机制，特别是突触抑制。在这里，我们研究了Rap在神经元形态发生和突触传递中的作用。Rap 2在海马锥体神经元中的表达使轴突和树突分支的长度和复杂性降低。此外，Rap 2导致树突棘和棘状突触的丢失，以及丝状伪足样突起和轴突触的增加。这些Rap 2形态学的影响是不存在的刺状中间神经元。与此相反，组成型活性Rap 1轴突或树突形态没有显着的影响。显性负Rap突变体增加了树突长度，表明内源性Rap抑制了树突的生长。α-氨基-3-羟基-5-甲基异恶唑-4-丙酸酯（AMPA）介导的微型兴奋性突触后电流（mEPSC）的幅度和频率降低与活性Rap 1或Rap 2转染海马神经元，与AMPA受体亚基GluR 2的表面和总水平降低。最后，GABA（A）受体拮抗剂增加突触活性抵消了Rap 2对树突生长的抑制作用，并掩盖了Rap 1和Rap 2对AMPA介导的mEPSC的作用。因此，Rap 1和Rap 2具有重叠但不同的作用，可能将突触传递的抑制与轴突和树突的收缩联系起来。
The Rap family of small GTPases is implicated in the mechanisms of synaptic plasticity, particularly synaptic depression. Here we studied the role of Rap in neuronal morphogenesis and synaptic transmission in cultured neurons. Constitutively active Rap2 expressed in hippocampal pyramidal neurons caused decreased length and complexity of both axonal and dendritic branches. In addition, Rap2 caused loss of dendritic spines and spiny synapses, and an increase in filopodia-like protrusions and shaft synapses. These Rap2 morphological effects were absent in aspiny interneurons. In contrast, constitutively active Rap1 had no significant effect on axon or dendrite morphology. Dominant-negative Rap mutants increased dendrite length, indicating that endogenous Rap restrains dendritic outgrowth. The amplitude and frequency of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-mediated miniature excitatory postsynaptic currents (mEPSCs) decreased in hippocampal neurons transfected with active Rap1 or Rap2, associated with reduced surface and total levels of AMPA receptor subunit GluR2. Finally, increasing synaptic activity with GABA(A) receptor antagonists counteracted Rap2's inhibitory effect on dendrite growth, and masked the effects of Rap1 and Rap2 on AMPA-mediated mEPSCs. Rap1 and Rap2 thus have overlapping but distinct actions that potentially link the inhibition of synaptic transmission with the retraction of axons and dendrites.