果蠅體內(nèi)調(diào)控細胞命運的重要蛋白質(zhì)Miranda的調(diào)控過程，并不像科學家想象中那么復雜。美國俄勒岡大學（University of Oregon）研究人員發(fā)現(xiàn)有一種非典型蛋白激酶C（aPKC）參與并獨立決定子代細胞的分化方向,。生化學家Kenneth Prehoda表示，在干細胞分裂時,，其含有aPKC 的一側(cè)或皮質(zhì)區(qū)域仍以干細胞形式存在,，而含有Miranda 的其他區(qū)域則分化為其他類型的細胞，如組成中樞神經(jīng)系統(tǒng)的神經(jīng)細胞,。相關(guān)機制發(fā)表在5月12日出版的Current Biology雜志上,。
論文指出，與眾多科學人員理論推測的不同,，干細胞分裂并非復雜的蛋白失活級聯(lián)過程,，而是一種被稱為ATP的高能核苷在aPKC的催化下脫去一分子磷酸，脫去的磷酸分子繼而又在aPKC的催化下與Miranda結(jié)合,。這個過程使Miranda與aPKC脫離,，并決定子細胞的分化方向。Prehoda 從生化角度上進行解釋認為,，Miranda在aPKC作用下磷酸化,，轉(zhuǎn)化為失活底物，并將其推向細胞的其他區(qū)域。
這篇文章的大部分內(nèi)容著眼于一些復雜理論的不確切之處,。Prehoda指出,，對于干細胞的分裂機制存在許多觀點，但大多數(shù)理論很復雜且難以解釋,。新的發(fā)現(xiàn)給出一個更簡單的機制,，而且許多其他類型細胞的分裂機制也可能與此類似。研究人員表示,，極性如何產(chǎn)生是一個基本的研究問題,。只有了解極性產(chǎn)生的機制，才能找到合理的方法用于干細胞的特定治療,。(生物谷Bioon.com)
生物谷推薦原始出處：
Current Biology, 16 April 2009 doi:10.1016/j.cub.2009.03.056
aPKC Phosphorylates Miranda to Polarize Fate Determinants during Neuroblast Asymmetric Cell Division
Scott X. Atwood1andKenneth E. Prehoda1,,
1 Institute of Molecular Biology and Department of Chemistry, University of Oregon, Eugene, OR 97403, USA
Summary
Asymmetric cell divisions generate daughter cells with distinct fates by polarizing fate determinants into separate cortical domains. Atypical protein kinase C (aPKC) is an evolutionarily conserved regulator of cell polarity. In Drosophila neuroblasts, apically restricted aPKC is required for segregation of neuronal differentiation factors such as Numb and Miranda to the basal cortical domain. Whereas Numb is polarized by direct aPKC phosphorylation, Miranda asymmetry is thought to occur via a complicated cascade of repressive interactions (aPKC | Lgl | myosin II | Miranda).Here we provide biochemical, cellular, and genetic data showing that aPKC directly phosphorylates Miranda to exclude it from the cortex and that Lgl antagonizes this activity. Miranda is phosphorylated by aPKC at several sites in its cortical localization domain and phosphorylation is necessary and sufficient for cortical displacement, suggesting that the repressive-cascade model is incorrect. In investigating key results that led to this model, we found that Y-27632, a Rho kinase inhibitor used to implicate myosin II, efficiently inhibits aPKC. Lgl3A, a nonphosphorylatable Lgl variant used to implicate Lgl in this process, inhibits the formation of apical aPKC crescents in neuroblasts. Furthermore, Lgl directly inhibits aPKC kinase activity.Miranda polarization during neuroblast asymmetric cell division occurs by displacement from the apical cortex by direct aPKC phosphorylation. Rather than mediating Miranda cortical displacement, Lgl instead promotes aPKC asymmetry by regulating its activity. The role of myosin II in neuroblast polarization, if any, is unknown.
