一些蛋白裝配成極性復(fù)合物,，然后定位在神經(jīng)母細(xì)胞的末端幫助指導(dǎo)其進(jìn)行不對(duì)稱分裂。但是這種機(jī)制目前我們尚不清楚,，近日,，來(lái)自日本理化研究所的生物學(xué)家通過(guò)對(duì)發(fā)育的果蠅胚胎中進(jìn)行研究，發(fā)現(xiàn)了指導(dǎo)這些蛋白定位在神經(jīng)母細(xì)胞上的主要調(diào)控子,。相關(guān)研究成果刊登在了近日的國(guó)際雜志Development Cell上,。
研究者Fumio Matsuzaki和他的研究團(tuán)隊(duì)篩選了神經(jīng)母細(xì)胞極性缺失的果蠅胚胎突變體，揭示了一個(gè)重要的在內(nèi)胚層發(fā)現(xiàn)的基因---Tre1,，該基因可以編碼跨膜的受體蛋白,，研究者在果蠅中剔除掉了該基因，結(jié)果顯示這種跨膜的受體蛋白對(duì)于垂直定向這種蛋白復(fù)合體的極性必不可少,。
更深入地研究蛋白與蛋白之間相互作用揭示了Tre1可以通過(guò)一些列的蛋白中介體來(lái)募集以及定向這種關(guān)鍵的極性復(fù)合物Par,，首先，Tre1可以激活一系列重要的信號(hào)轉(zhuǎn)換分子來(lái)募集蛋白質(zhì)Pins，Pins可以調(diào)節(jié)主軸定位,；另外一種蛋白inscuteable在Pins和Par之間扮演著分子連接的作用,，以確保每一個(gè)組分都能夠得到合適的定位。
研究者表示,，這種Par復(fù)合物可以調(diào)節(jié)包括神經(jīng)細(xì)胞和干細(xì)胞在內(nèi)的一系列細(xì)胞的細(xì)胞極性的形成,，因此這個(gè)過(guò)程涉及到不同細(xì)胞在其發(fā)育階段的極性的取向。隨著Tre1的出現(xiàn),，同時(shí)也可以控制神經(jīng)母細(xì)胞極性復(fù)合物的取向,，研究者正在極力去尋找其調(diào)節(jié)子，目前研究者并不知道哪些分子扮演著表皮細(xì)胞外來(lái)信號(hào)分子的角色,，因此,，研究團(tuán)隊(duì)也將會(huì)研究是否這種觀察到的機(jī)制是通過(guò)進(jìn)化而來(lái)的，并且是否也適用于哺乳動(dòng)物的神經(jīng)干細(xì)胞,。（生物谷：T.Shen編譯）
doi:10.1016/j.devcel.2011.10.027
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Tre1 GPCR Signaling Orients Stem Cell Divisions in the Drosophila Central Nervous System
Shigeki Yoshiura, Nao Ohta, Fumio Matsuzaki
During development, directional cell division is a major mechanism for establishing the orientation of tissue growth. Drosophila neuroblasts undergo asymmetric divisions perpendicular to the overlying epithelium to produce descendant neurons on the opposite side, thereby orienting initial neural tissue growth. However, the mechanism remains elusive. We provide genetic evidence that extrinsic GPCR signaling determines the orientation of cortical polarity underlying asymmetric divisions of neuroblasts relative to the epithelium. The GPCR Tre1 activates the G protein oα subunit in neuroblasts by interacting with the epithelium to recruit Pins, which regulates spindle orientation. Because Pins associates with the Par-complex via Inscuteable, Tre1 consequently recruits the polarity complex to orthogonally orient the polarity axis to the epithelium. Given the universal role of the Par complex in cellular polarization, we propose that the GPCR-Pins system is a comprehensive mechanism controlling tissue polarity by orienting polarized stem cells and their divisions.
