当前位置: X-MOL 学术Mol. Neurobiol. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Interaction Between CRIPT and PSD-95 Is Required for Proper Dendritic Arborization in Hippocampal Neurons.
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2020-03-09 , DOI: 10.1007/s12035-020-01895-5
Anton Omelchenko 1, 2 , Harita Menon 1 , Sarah G Donofrio 1 , Gaurav Kumar 1 , Heidi M Chapman 3 , Joshua Roshal 1 , Eduardo R Martinez-Montes 1 , Tiffany L Wang 3 , Mark R Spaller 3 , Bonnie L Firestein 1
Affiliation  

CRIPT, the cysteine-rich PDZ-binding protein, binds to the third PDZ domain of PSD-95 (postsynaptic density protein 95) family proteins and directly binds microtubules, linking PSD-95 family proteins to the neuronal cytoskeleton. Here, we show that overexpression of a full-length CRIPT leads to a modest decrease, and knockdown of CRIPT leads to an increase in dendritic branching in cultured rat hippocampal neurons. Overexpression of truncated CRIPT lacking the PDZ domain-binding motif, which does not bind to PSD-95, significantly decreases dendritic arborization. Conversely, overexpression of a full-length CRIPT significantly increases the number of immature and mature dendritic spines, and this effect is not observed when CRIPT∆PDZ is overexpressed. Competitive inhibition of CRIPT binding to the third PDZ domain of PSD-95 with PDZ3-binding peptides resulted in differential effects on dendritic arborization based on the origin of respective peptide sequence. These results highlight multifunctional roles of CRIPT during development and underscore the significance of the interaction between CRIPT and the third PDZ domain of PSD-95.

中文翻译:


CRIPT 和 PSD-95 之间的相互作用是海马神经元正确树突状树枝化所必需的。



CRIPT 是富含半胱氨酸的 PDZ 结合蛋白,可与 PSD-95(突触后密度蛋白 95)家族蛋白的第三个 PDZ 结构域结合,并直接结合微管,将 PSD-95 家族蛋白与神经元细胞骨架连接起来。在这里,我们发现全长 CRIPT 的过度表达会导致培养的大鼠海马神经元树突分支的适度减少,而 CRIPT 的敲低会导致树突分支的增加。缺乏 PDZ 结构域结合基序(不与 PSD-95 结合)的截短 CRIPT 的过表达会显着减少树突分枝。相反,全长 CRIPT 的过表达会显着增加未成熟和成熟树突棘的数量,而当 CRIPTΔPDZ 过表达时,不会观察到这种效应。用 PDZ3 结合肽竞争性抑制 CRIPT 与 PSD-95 第三个 PDZ 结构域的结合,导致基于各自肽序列的起源对树突分枝产生不同的影响。这些结果突出了 CRIPT 在发育过程中的多功能作用,并强调了 CRIPT 与 PSD-95 第三个 PDZ 结构域之间相互作用的重要性。
更新日期:2020-04-22
down
wechat
bug