美國(guó)麻省理工學(xué)院的研究人員確定出了一個(gè)對(duì)正常大腦功能至關(guān)重要的交流網(wǎng)絡(luò)形成非常關(guān)鍵的蛋白質(zhì)家族,。這項(xiàng)研究的結(jié)果分兩部分刊登在11月11的《神經(jīng)元》（Neuron）雜志和11月18日的《自然—細(xì)胞生物學(xué)》（Nature Cell Biology）雜志的網(wǎng)絡(luò)版上,。
這個(gè)由Frank Gertler教授領(lǐng)導(dǎo)的研究組發(fā)現(xiàn),，一個(gè)特殊的蛋白質(zhì)家族是指導(dǎo)軸突和樹突形成所必須的,。軸突和樹突都是方便神經(jīng)元間交流的細(xì)胞延伸物,。
這項(xiàng)研究主要對(duì)細(xì)胞外延物——神經(jīng)突(軸突和樹突的前體)了解神經(jīng)突如何形成最終將有助于找到可刺激神經(jīng)突生長(zhǎng)的療法。研究人員構(gòu)建出首個(gè)能夠用于研究這個(gè)叫做Ena/VASP蛋白家族功能的模型,。
大腦皮層中的大部分神經(jīng)元都由一個(gè)單獨(dú)的長(zhǎng)軸突（將信息傳遞給其他細(xì)胞）和多個(gè)較短的樹突（接收來自其他細(xì)胞的信息）,。這些軸突和樹突的相互連接是形成一個(gè)功能神經(jīng)元環(huán)路的關(guān)鍵。
在這項(xiàng)新的研究中,，研究人員發(fā)現(xiàn)沒有三種Ena/VASP蛋白的小鼠雖然能制造腦細(xì)胞,，但是那些神經(jīng)元卻不能延伸出任何軸突或樹突。
已經(jīng)知道Ena/VASP蛋白與軸突的導(dǎo)航（延伸方向的確定）有關(guān),，但是研究人員驚訝地發(fā)現(xiàn)它們還對(duì)神經(jīng)突的形成至關(guān)重要,。
Ena/VASP蛋白定位在神經(jīng)突絲（絲狀偽足）的頂端。這些指令告訴細(xì)胞是否繼續(xù)延伸絲狀偽足或停止生長(zhǎng),。沒有Ena/VASP蛋白,，神經(jīng)突就不能形成，因此神經(jīng)元間也不能形成連接,。
研究人員認(rèn)為,，Ena/VASP蛋白通過調(diào)節(jié)肌動(dòng)蛋白絲與細(xì)胞中微管的相互作用來控制絲狀偽足的生長(zhǎng)。一個(gè)推理就是微管可能通過肌動(dòng)蛋白絲來傳遞物質(zhì)或信號(hào)給絲狀偽足,。
原始出處:
Neuron, Vol 56, 441-455, 08 November 2007
Article
Ena/VASP Is Required for Neuritogenesis in the Developing Cortex
Adam V. Kwiatkowski,1,5,6 Douglas A. Rubinson,1,5 Erik W. Dent,1,7 J. Edward van Veen,1 Jonathan D. Leslie,1 Jiangyang Zhang,2 Leslie M. Mebane,1 Ulrike Philippar,1 Elaine M. Pinheiro,1 Aurora A. Burds,1 Roderick T. Bronson,3 Susumu Mori,2 Reinhard Fässler,4 and Frank B. Gertler3,
1 Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
2 Department of Radiology, Division of Nuclear Magnetic Resonance Research, Johns Hopkins University School of Medicine, Baltimore, MD 2120, USA
3 Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, North Grafton, MA 01536, USA
4 Department of Molecular Medicine, Max-Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Germany
Corresponding author
Frank B. Gertler
[email protected]
Mammalian cortical development involves neuronal migration and neuritogenesis; this latter process forms the structural precursors to axons and dendrites. Elucidating the pathways that regulate the cytoskeleton to drive these processes is fundamental to our understanding of cortical development. Here we show that loss of all three murine Ena/VASP proteins, a family of actin regulatory proteins, causes neuronal ectopias, alters intralayer positioning in the cortical plate, and, surprisingly, blocks axon fiber tract formation during corticogenesis. Cortical fiber tract defects in the absence of Ena/VASP arise from a failure in neurite initiation, a prerequisite for axon formation. Neurite initiation defects in Ena/VASP-deficient neurons are preceded by a failure to form bundled actin filaments and filopodia. These findings provide insight into the regulation of neurite formation and the role of the actin cytoskeleton during cortical development.
