β-arrestins是一個(gè)蛋白質(zhì)家族,，對于調(diào)節(jié)訊息傳導(dǎo)扮演很重要的角色,，在哺乳動物細(xì)胞中,，β-Arrestins在神經(jīng)系統(tǒng)和淋巴系統(tǒng)中分布最多，呈現(xiàn)出廣泛表達(dá)的特征,。它們主要作為G蛋白偶聯(lián)受體(GPCR)信號的負(fù)調(diào)節(jié)因子,在受體脫敏,、受體內(nèi)吞、蛋白酶體途徑降解,、細(xì)胞凋亡以及多種細(xì)胞信號轉(zhuǎn)導(dǎo)中起著重要的作用,。
但是在大腦生理學(xué)方面，β-arrestins研究的比較少,，許多相關(guān)的功能都還屬于空白區(qū)域,，在復(fù)旦大學(xué)馬蘭教授領(lǐng)導(dǎo)的研究小組發(fā)表的最新文章中，研究人員發(fā)現(xiàn)β-arrestins蛋白家族β-arrestins-2在形成大腦恐怖記憶,，以及杏仁核突觸可塑性方面扮演了重要的角色,，這對于進(jìn)一步了解β-arrestins功能，以及大腦恐怖記憶研究具有重要的意義,。
β-arrestin-2與β-arrestin-1一樣，廣泛存在于各種細(xì)胞中,，調(diào)節(jié)絕大多數(shù)G蛋白偶聯(lián)受體(GPCR)的活性,。研究顯示，大腦在應(yīng)對恐怖信息的時(shí)候,，β-arrestin-2能轉(zhuǎn)移至杏仁核細(xì)胞膜,，與PDE-4——一種cAMP降解酶相互作用，抑制PKA活性,。
通過進(jìn)一步的實(shí)驗(yàn),，研究人員還發(fā)現(xiàn)Arrb2－/－小鼠的側(cè)杏仁核突觸會條件型恐怖記憶和長時(shí)程記憶增選受損，而且這種突變型不能結(jié)合PDE-4,，恢復(fù)基礎(chǔ)PKA活性,，以及保全條件型恐怖記憶。
總而言之,，這些數(shù)據(jù)表明β-arrestin-2和PDE-4復(fù)合物能激活杏仁核PKA活性,，這一反饋調(diào)控對于條件型恐怖記憶的形成具有重要意義。（生物谷Bioon.com）
Nature：恐怖記憶可通過重演消除
生物谷推薦原始出處：
PNAS December 2, 2009, doi: 10.1073/pnas.0906941106
Regulation of amygdalar PKA by β-arrestin-2/phosphodiesterase-4 complex is critical for fear conditioning
Yuting Lia,b,1, Haohong Lia,1, Xing Liua,1, Guobin Baoa, Yezheng Taoa, Ziyan Wua, Peng Xiaa, Chunfu Wub, Baoming Lia and Lan Maa,2
aThe State Key Laboratory of Medical Neurobiology, Shanghai Medical College and Institutes of Brain Science, Fudan University, Shanghai 200032, China; and
bDepartment of Pharmacology, Shenyang Pharmaceutical University, Shenyang 110016, China
β-arrestins, key regulators of receptor signaling, are highly expressed in the central nervous system, but their roles in brain physiology are largely unknown. Here we show that β-arrestin-2 is critically involved in the formation of associative fear memory and amygdalar synaptic plasticity. In response to fear conditioning, β-arrestin-2 translocates to amygdalar membrane where it interacts with PDE-4, a cAMP-degrading enzyme, to inhibit PKA activation. Arrb2?/? mice exhibit impaired conditioned fear memory and long-term potentiation at the lateral amygdalar synapses. Moreover, expression of the β-arrestin-2 in the lateral amygdala of Arrb2-/- mice, but not its mutant form that is incapable of binding PDE-4, restores basal PKA activity and rescues conditioned fear memory. Taken together, our data demonstrate that the feedback regulation of amygdalar PKA activation by β-arrestin-2 and PDE-4 complex is critical for the formation of conditioned fear memory.
