來自MIT的Picower學(xué)習(xí)和記憶研究所的科學(xué)家最近發(fā)現(xiàn)了一種常見蛋白在大腦中出人意料的功能,,這一發(fā)現(xiàn)將可能帶來治療阿茲海默癥和帕金森氏癥等疾病的新方法,。
神經(jīng)科學(xué)教授,、Howard Hughes醫(yī)學(xué)研究所科學(xué)家Morgan H. Sheng以及同事將他們的研究結(jié)果發(fā)表在10月23日的《當(dāng)代生物學(xué)》(Current Biology)上,,文章表示,幫助酵母細(xì)胞出芽生殖成兩個(gè)后代酵母菌的蛋白同樣也能幫助神經(jīng)萌芽出突起,,這能用來與周圍神經(jīng)元交流,。
科學(xué)家早在1970年代就已經(jīng)知道這種septin蛋白對(duì)于酵母菌細(xì)胞質(zhì)的分裂過程很關(guān)鍵。Sheng表示:“在酵母中,,septin位于母細(xì)胞和芽體之間的狹窄位置,。令人驚訝的是我們發(fā)現(xiàn)septin還存在于神經(jīng)樹突棘的同樣位置以及樹突的支點(diǎn)。”
哺乳動(dòng)物中發(fā)現(xiàn)的14種septin有9種存在于大腦中,。其中之一Sept7最常出現(xiàn),,但它的功能卻并不清楚。Septin形成長(zhǎng)長(zhǎng)的細(xì)絲,,并利用其它蛋白來構(gòu)建細(xì)胞的基礎(chǔ)結(jié)構(gòu),。盡管神經(jīng)元不會(huì)分裂,但是它們能形成突起,,并最終延長(zhǎng)成為樹突,。樹突負(fù)責(zé)將其它神經(jīng)元的電刺激傳遞到所屬的神經(jīng)胞體。
電刺激通過突觸傳播,,突觸位于樹突上的不同位置,。樹突對(duì)于接受突觸信號(hào)很重要。合作者之一的Tomoko Tada說:“由于樹突棘對(duì)于突觸功能和記憶形成很重要,,了解septin能幫助防止很多神經(jīng)退化疾病導(dǎo)致的樹突棘和突觸損失,。Septin可能是治療以上疾病的目標(biāo)之一。”
此外在科學(xué)家培養(yǎng)的海馬體神經(jīng)元中,,septin對(duì)于正常的突起和棘形成很關(guān)鍵,。充足的septin能幫助樹突生長(zhǎng)增生,而缺少septin則使它們變得很小,、畸形,。Sheng說:“提高septin的表達(dá)和功能將增加棘和突觸的穩(wěn)定性,這對(duì)于學(xué)習(xí)和記憶等認(rèn)知功能有好處,。”實(shí)驗(yàn)室目前正在探索防止septin退化和損失的方法,。(教育部科技發(fā)展中心 )
原文鏈接:http://www.physorg.com/news112020162.html
原始出處:
Current Biology, Vol 17, 1752-1758, 23 October 2007
Report
Role of Septin Cytoskeleton in Spine Morphogenesis and Dendrite Development in Neurons
Tomoko Tada,1 Alyson Simonetta,1 Matthew Batterton,1 Makoto Kinoshita,2 Dieter Edbauer,1 and Morgan Sheng1,
1 The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139
2 Biochemistry and Cell Biology Unit, Horizontal Medical Research Organization, Kyoto University Graduate School of Medicine, Yoshida Konoe, Sakyo, Kyoto 606-8501, Japan
Corresponding author
Morgan Sheng
[email protected]
Septins are GTP-binding proteins that polymerize into heteromeric filaments and form microscopic bundles or ring structures in vitro and in vivo. Because of these properties and their ability to associate with membrane, F-actin, and microtubules, septins have been generally regarded as cytoskeletal components [1, 2]. Septins are known to play roles in cytokinesis, in membrane trafficking, and as structural scaffolds; however, their function in neurons is poorly understood. Many members of the septin family, including Septin 7 (Sept7), were found by mass-spectrometry analysis of postsynaptic density (PSD) fractions of the brain [3, 4], suggesting a possible postsynaptic function of septins in neurons. We report that Sept7 is localized at the base of dendritic protrusions and at dendritic branch points in cultured hippocampal neurons—a distribution reminiscent of septin localization in the bud neck of budding yeast. Overexpression of Sept7 increased dendrite branching and the density of dendritic protrusions, whereas RNA interference (RNAi)-mediated knockdown of Sept7 led to reduced dendrite arborization and a greater proportion of immature protrusions. These data suggest that Sept7 is critical for spine morphogenesis and dendrite development during neuronal maturation.