Opposing functions of CREB and MKK1 synergistically regulate the geometry of dendritic spines in visual cortex.
Opposing functions of CREB and MKK1 synergistically regulate the geometry of dendritic spines in visual cortex.
复制标题
CREB 和 MKK1 的相反功能协同调节视觉皮层树突棘的几何形状。
DOI：
10.1002/cne.21424
复制
发表时间：
2007
期刊：
影响因子：
--
通讯作者：
Pham,TonyA
中科院分区：
文献类型：
--
作者：
Suzuki,Seigo;Zhou,Hongyi;Neumaier,JohnF;Pham,TonyA
大多数对锥体神经元的兴奋性输入是在树突棘上产生的。树突棘的几何结构调节突触功能；然而，我们对调节脊柱几何形状的分子信号知之甚少。在这里，我们报告了神经元通过一个需要转录因子CREB和激酶MKK1的过程来协调调节脊柱的几何形状以补偿脊柱数量的变化。我们发现CREB功能通过活性阻断被诱导，而MKK1则被抑制。为了获得CREB和MKK1在体内调节树突脊柱几何形状的证据，我们在完整大鼠视觉皮层锥体神经元中共表达绿色荧光蛋白和显性阴性CREB或MKK1。然后用共聚焦显微镜观察第3层神经元顶端树突上的棘。我们发现CREB和MKK1以相反的方式调节脊柱的几何形状。当脊柱密度高时，需要MKK1来减小脊柱头的大小，而当脊柱密度低时，需要CREB来扩大脊柱。我们的数据表明，CREB和MKK1可能是互补的负反馈机制，以维持突触驱动在一定范围内。[j]中华神经医学杂志，2006,31(3):557 - 557。©2007 Wiley‐Liss, Inc。
Most excitatory inputs onto pyramidal neurons are made on dendritic spines. The geometry of dendritic spines modulates synaptic function; yet we know little regarding the molecular signals that regulate spine geometry. Here we report that neurons coordinately regulate the geometry of spines to compensate for variability in spine number, by a process requiring the transcription factor CREB and the kinase MKK1. We find that CREB function is induced, whereas MKK1 is inhibited, by activity blockade. To obtain evidence that CREB and MKK1 regulate dendritic spine geometry in vivo, we coexpressed green fluorescent protein and dominant negative CREB or MKK1 in pyramidal neurons of the intact rat visual cortex. Spines on apical dendrites of layer 3 neurons were then characterized by confocal microscopy. We find that CREB and MKK1 regulate spine geometry in opposite ways. MKK1 is required to reduce spine head size when spine density is high, whereas CREB is required to enlarge spines when spine density is low. Our data suggest that CREB and MKK1 might function as complementary negative feedback mechanisms to maintain synaptic drive within bounds. J. Comp. Neurol. 503:605–617, 2007. © 2007 Wiley‐Liss, Inc.