Celsr3 is required for Purkinje cell maturation and regulates cerebellar postsynaptic plasticity.
Celsr3 is required for Purkinje cell maturation and regulates cerebellar postsynaptic plasticity.
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Celsr3 是浦肯野细胞成熟所必需的，并调节小脑突触后可塑性
DOI：
10.1016/j.isci.2021.102812
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发表时间：
2021-07-23
期刊：
影响因子：
5.8
通讯作者：
Zhou L
中科院分区：
文献类型：
--
作者：
Zhou Q;Qin J;Liang Y;Zhang W;He S;Tissir F;Qu Y;Zhou L
非典型钙粘蛋白Celsr 3对脑胚胎发育至关重要，其在出生后小脑中的作用尚不清楚。使用Celsr 3-GFP小鼠，Celsr 3在出生后浦肯野细胞（PC）中显示高表达。出生后PC中Celsr 3的条件性敲除（cKO）小鼠表现出运动协调和学习的缺陷、萎缩的PC树突和减少的突触。小脑切片中的全PC记录揭示了Celsr 3 cKO突变体中mEPSC和突触后可塑性（LTP和LTD）缺陷的频率降低。Wnt 5a灌注增强LTP形成，在对照中，其可被cAMP激动剂阻断，并被cAMP拮抗剂减少，但在Celsr 3 cKO或Fzd 3 cKO小脑切片中不存在。与对照组相比，Celsr 3 cKO可使mGluR 1激动剂诱导的LTD和配对刺激诱导的PC树突PKCα过表达失败，mGluR 1表达下调。综上所述，Celsr 3是PC成熟所必需的，并分别通过Wnt 5a/cAMP和mGluR 1/PKCα信号通路调节突触后LTP和LTD。出生后PC中的Celsr 3 cKO损害小鼠运动协调和学习Celsr 3失活影响PC树突和突触的成熟Celsr 3是通过Wnt 5a/cAMP信号传导诱导小脑LTP所必需的Celsr 3通过mGluR 1/PKCα途径调节小脑LTD诱导发育神经科学;认知神经科学
Atypical cadherin Celsr3 is critical for brain embryonic development, and its role in the postnatal cerebellum remains unknown. Using Celsr3-GFP mice, Celsr3 shows high expression in postnatal Purkinje cells (PCs). Mice with conditional knockout (cKO) of Celsr3 in postnatal PCs exhibit deficit in motor coordination and learning, atrophic PC dendrites, and decreased synapses. Whole-PC recording in cerebellar slices discloses a reduction frequency of mEPSC and defective postsynaptic plasticity (LTP and LTD) in Celsr3 cKO mutants. Wnt5a perfusion enhances LTP formation, which could be occluded by cAMP agonist and diminished by cAMP antagonist in control, but not in Celsr3 cKO or Fzd3 cKO cerebellar slices. Celsr3 cKO resulted in the failure of mGluR1 agonist-induced LTD and paired stimulation-induced PKCα overexpression in PC dendrites, and downregulation of mGluR1 expression compvared to controls. In conclusion, Celsr3 is required for PCs maturation and regulates postsynaptic LTP and LTD through Wnt5a/cAMP and mGluR1/PKCα signaling respectively. Celsr3 cKO in postnatal PCs impairs mouse motor coordination and learning Celsr3 inactivation affects the maturation of PC dendrites and synapses Celsr3 is required for the cerebellar LTP induction via the Wnt5a/cAMP signaling Celsr3 regulates the cerebellar LTD induction through the mGluR1/PKCα pathway Developmental neuroscience; Cognitive neuroscience
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DOI：
10.2183/pjab.89.183
发表时间：
2013
期刊：
Proceedings of the Japan Academy. Series B, Physical and biological sciences
影响因子：
--
作者：
Hirano T
通讯作者：
Hirano T
影响因子：
5.5
作者：
ITO, M;SAKURAI, M;TONGROACH, P
通讯作者：
TONGROACH, P
影响因子：
64.5
作者：
AIBA, A;CHEN, C;TONEGAWA, S
通讯作者：
TONEGAWA, S
DOI：
10.1523/jneurosci.6311-10.2011
发表时间：
2011-06-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Cerpa W;Gambrill A;Inestrosa NC;Barria A
通讯作者：
Barria A
非典型钙粘蛋白 Celsr3 在海马成熟和连接中的作用
影响因子：
5.3
作者：
Feng, Jia;Xu, Ying;Zhou, Libing
通讯作者：
Zhou, Libing