Postsynaptic PDLIM5/Enigma Homolog binds SPAR and causes dendritic spine shrinkage.
Postsynaptic PDLIM5/Enigma Homolog binds SPAR and causes dendritic spine shrinkage.
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DOI：
10.1016/j.mcn.2009.10.009
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发表时间：
2010-02
影响因子：
3.5
通讯作者：
Pak, Daniel T. S.
中科院分区：
文献类型：
--
作者：
Herrick, Scott;Evers, Danielle M.;Lee, Ji-Yun;Udagawa, Noriko;Pak, Daniel T. S.
树突棘的形态在突触发育和可塑性中起重要作用，树突棘的形态紊乱与多种神经系统疾病有关。在这里，我们确定了Spine-Associated RapGAP（SPAR），一种重组肌动蛋白细胞骨架并驱动树突棘头生长的突触后蛋白，和PDZ-LIM（postsynaptic density-95/Discs large/Escherichoccludens 1-Lin 11/Isl-1/Mec 3）家族成员PDLIM 5/ Enigma Homolog（ENH）之间的相互作用。PDLIM 5与双相情感障碍、重性抑郁症和精神分裂症的易感性有关，但其在神经系统疾病中的功能知之甚少。我们发现PDLIM 5存在于突触后致密区，在那里它促进树突棘头部尺寸减小和更长的丝状伪足样形态。相反，针对PDLIM 5的RNA干扰或PDLIM 5与SPAR相互作用的丧失导致棘头直径增加。此外，PKC激活促进PDLIM 5向树突棘的递送，并增加其与SPAR的棘共定位。这些数据揭示了PDLIM 5在树突棘收缩中的新的突触后功能，这可能与其与精神疾病的相关性有关。
Dendritic spine morphology is thought to play important roles in synaptic development and plasticity, and morphological derangements in spines are correlated with several neurological disorders. Here, we identified an interaction between Spine-Associated RapGAP (SPAR), a postsynaptic protein that reorganizes actin cytoskeleton and drives dendritic spine head growth, and PDLIM5 / Enigma Homolog (ENH), a PDZ-LIM (postsynaptic density-95/Discs large/zona occludens 1-Lin11/Isl-1/Mec3) family member. PDLIM5 has been implicated in susceptibility to bipolar disorder, major depression and schizophrenia but its function in neurological disease is poorly understood. We show that PDLIM5 is present in the postsynaptic density, where it promotes decreased dendritic spine head size and longer, filopodia-like morphology. Conversely, RNA interference against PDLIM5 or loss of PDLIM5 interaction with SPAR caused increased spine head diameter. Furthermore, PKC activation promoted delivery of PDLIM5 into dendritic spines and increased its spine colocalization with SPAR. These data reveal new postsynaptic functions for PDLIM5 in shrinkage of dendritic spines that may be relevant to its association with psychiatric illness.
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DOI：
10.1016/j.bbrc.2009.04.069
发表时间：
2009-06-19
影响因子：
3.1
作者：
Hoe, Hyang-Sook;Lee, Ji-Yun;Pak, Daniel T. S.
通讯作者：
Pak, Daniel T. S.
影响因子：
64.5
作者：
ABELIOVICH, A;CHEN, C;TONEGAWA, S
通讯作者：
TONEGAWA, S
影响因子：
3.5
作者：
Iwamoto, K;Bundo, M;Kato, T
通讯作者：
Kato, T
影响因子：
9.8
作者：
Gurling, HMD;Kalsi, G;Curtis, D
通讯作者：
Curtis, D
影响因子：
64.8
作者：
KIM, E;NIETHAMMER, M;SHENG, M
通讯作者：
SHENG, M