據(jù)刊登在9月4日Cell雜志的封面文章，北卡羅萊納大學(xué)的研究人員現(xiàn)在發(fā)現(xiàn),，大腦發(fā)育形成神經(jīng)網(wǎng)絡(luò)的過程中,，大量的神經(jīng)元必須要遷移到正確的位置，并與周圍神經(jīng)元構(gòu)成復(fù)雜的突觸連接,。一旦該過程出錯,，則會導(dǎo)致精神發(fā)育遲滯，誦讀困難,，自閉癥等精神障礙,。
之前的研究認(rèn)為，細(xì)胞形變或移動是通過細(xì)胞骨架活動形成的,。但該研究結(jié)果表明,，大腦發(fā)育過程中腦蛋白srGAP2可以直接通過彎曲細(xì)胞膜，使細(xì)胞發(fā)生形變形成絲狀偽足(filopodia),。但這種srGAP2蛋白是出現(xiàn)在3p-綜合癥(3p- syndrome)的蛋白質(zhì)家族的一員,。因此，該研究或許對研究這類精神障礙疾病具有重要意義,。
srGAP2基因在大腦發(fā)育過程中一直處于活躍表達(dá)狀態(tài),，srGAP2蛋白存在一個獨(dú)特的結(jié)構(gòu)域——F-BAR域,。研究人員利用電流在小鼠大腦切片導(dǎo)入能控制srGAP2蛋白F-BAR域活性的遺傳物質(zhì)。然后培養(yǎng)并觀察腦神經(jīng)元的動態(tài),。當(dāng)激活F-BAR域時,，研究人員發(fā)現(xiàn)神經(jīng)元形成阻止遷移的絲狀偽足。而當(dāng)減少該蛋白的表達(dá)水平時,，神經(jīng)元遷移的速度加快,，分支減少。
據(jù)研究人員介紹,，srGAP2蛋白F-BAR域與神經(jīng)元的分支數(shù)量密切相關(guān),，這些分支是神經(jīng)元之間相互聯(lián)系必要結(jié)構(gòu)。 (生物谷Bioon.com)
生物谷推薦原始出處：
Cell, Volume 138, Issue 5, 990-1004, 4 September 2009 doi:10.1016/j.cell.2009.06.047
The F-BAR Domain of srGAP2 Induces Membrane Protrusions Required for Neuronal Migration and Morphogenesis
Sabrice Guerrier1,2,Jaeda Coutinho-Budd3,Takayuki Sassa2,Aurélie Gresset1,Nicole Vincent Jordan1,Keng Chen4,Wei-Lin Jin4,Adam Frost5,6andFranck Polleux1,2,,
1 Department of Pharmacology, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
2 Neuroscience Research Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
3 Neurobiology Curriculum, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
4 Institute of Neurosciences, Shanghai Jiao Tong University, Shanghai 200240, China
5 Department of Molecular Biophysics and Biochemistry, Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT 06510, USA
During brain development, proper neuronal migration and morphogenesis is critical for the establishment of functional neural circuits. Here we report that srGAP2 negatively regulates neuronal migration and induces neurite outgrowth and branching through the ability of its F-BAR domain to induce filopodia-like membrane protrusions resembling those induced by I-BAR domains invivo and invitro. Previous work has suggested that in nonneuronal cells filopodia dynamics decrease the rate of cell migration and the persistence of leading edge protrusions. srGAP2 knockdown reduces leading process branching and increases the rate of neuronal migration invivo. Overexpression of srGAP2 or its F-BAR domain has the opposite effects, increasing leading process branching and decreasing migration. These results suggest that F-BAR domains are functionally diverse and highlight the functional importance of proteins directly regulating membrane deformation for proper neuronal migration and morphogenesis.
