JNK1 controls dendritic field size in L2/3 and L5 of the motor cortex, constrains soma size, and influences fine motor coordination.
JNK1 controls dendritic field size in L2/3 and L5 of the motor cortex, constrains soma size, and influences fine motor coordination.
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DOI：
10.3389/fncel.2014.00272
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发表时间：
2014
影响因子：
5.3
通讯作者：
Coffey ET
中科院分区：
文献类型：
--
作者：
Komulainen E;Zdrojewska J;Freemantle E;Mohammad H;Kulesskaya N;Deshpande P;Marchisella F;Mysore R;Hollos P;Michelsen KA;Mågard M;Rauvala H;James P;Coffey ET
JNK通路上的遗传异常赋予自闭症谱系障碍、精神分裂症和智力残疾的易感性。JNK信号传导功能的获得或丧失导致这些普遍的树突疾病以及相关的运动功能障碍的机制尚不清楚。在这里，我们发现JNK 1调节小鼠运动皮层（M1）的L2/3和L5锥体神经元的树突区，这是控制随意运动的主要兴奋性通路。在JNK 1-/-小鼠中，L5锥体神经元的基底树突分支在M1中增加，细胞索马大小也增加，而在L2/3中，树突分支减少。我们发现JNK 1磷酸化大鼠HMW-MAP 2的T1619，T1622和T1625（Uniprot P15146）对应于小鼠T1617，T1620，T1623，以创建一个结合基序，这是至关重要的MAP 2与微管的相互作用和稳定，树突生长控制。在T1619、T1622和T1625上假磷酸化的GFP-HMW-MAP 2在M1中的靶向表达增加了L2/3中的树突复杂性，表明HMW-MAP 2的JNK 1磷酸化调节树突场。与在L2/3和L5中观察到的形态学变化一致，JNK 1-/-小鼠在肢体放置和运动协调方面表现出缺陷，而在老年动物中步幅长度减少。总之，JNK 1磷酸化HMW-MAP 2以增加其微管的稳定性，同时控制M1的主要兴奋性通路中的树突状场。此外，JNK 1有助于精细运动协调的正常功能。我们报告的第一次，Sholl的树突结构的定量分析，并在JNK 1-/-小鼠的运动行为。我们的研究结果说明了中断JNK 1信号传导的分子和行为后果，并提供了新的地面机制的理解，这些流行的神经性精神疾病的JNK通路的遗传中断是中央。
Genetic anomalies on the JNK pathway confer susceptibility to autism spectrum disorders, schizophrenia, and intellectual disability. The mechanism whereby a gain or loss of function in JNK signaling predisposes to these prevalent dendrite disorders, with associated motor dysfunction, remains unclear. Here we find that JNK1 regulates the dendritic field of L2/3 and L5 pyramidal neurons of the mouse motor cortex (M1), the main excitatory pathway controlling voluntary movement. In Jnk1-/- mice, basal dendrite branching of L5 pyramidal neurons is increased in M1, as is cell soma size, whereas in L2/3, dendritic arborization is decreased. We show that JNK1 phosphorylates rat HMW-MAP2 on T1619, T1622, and T1625 (Uniprot P15146) corresponding to mouse T1617, T1620, T1623, to create a binding motif, that is critical for MAP2 interaction with and stabilization of microtubules, and dendrite growth control. Targeted expression in M1 of GFP-HMW-MAP2 that is pseudo-phosphorylated on T1619, T1622, and T1625 increases dendrite complexity in L2/3 indicating that JNK1 phosphorylation of HMW-MAP2 regulates the dendritic field. Consistent with the morphological changes observed in L2/3 and L5, Jnk1-/- mice exhibit deficits in limb placement and motor coordination, while stride length is reduced in older animals. In summary, JNK1 phosphorylates HMW-MAP2 to increase its stabilization of microtubules while at the same time controlling dendritic fields in the main excitatory pathway of M1. Moreover, JNK1 contributes to normal functioning of fine motor coordination. We report for the first time, a quantitative Sholl analysis of dendrite architecture, and of motor behavior in Jnk1-/- mice. Our results illustrate the molecular and behavioral consequences of interrupted JNK1 signaling and provide new ground for mechanistic understanding of those prevalent neuropyschiatric disorders where genetic disruption of the JNK pathway is central.
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DOI：
10.1083/jcb.138.5.1067
发表时间：
1997-09-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Felgner H;Frank R;Biernat J;Mandelkow EM;Mandelkow E;Ludin B;Matus A;Schliwa M
通讯作者：
Schliwa M
影响因子：
4.5
作者：
Broadbelt, K;Byne, W;Jones, LB
通讯作者：
Jones, LB
影响因子：
4
作者：
David, JP;Sabapathy, K;Wagner, EF
通讯作者：
Wagner, EF
影响因子：
5.3
作者：
Björkblom, B;Östman, N;Coffey, ET
通讯作者：
Coffey, ET
影响因子：
25
作者：
de Anda, Froylan Calderon;Rosario, Ana Lucia;Durak, Omer;Tran, Tracy;Graeff, Johannes;Meletis, Konstantinos;Rei, Damien;Soda, Takahiro;Madabhushi, Ram;Ginty, David D.;Kolodkin, Alex L.;Tsai, Li-Huei
通讯作者：
Tsai, Li-Huei