的啟發(fā)。其中描述了WHAMM(黃色),、高爾基網(wǎng)(紫色),、微管(白色)以及絲狀肌動蛋白(紅色)細(xì)胞骨架。圖片提供:Taro Ohkawa)
肌動蛋白纖維和微管在生物的膜輸運(yùn)過程中起到了重要的作用,,但是科學(xué)家很少能發(fā)現(xiàn)連接這兩種細(xì)胞骨架系統(tǒng)膜輸運(yùn)中間物質(zhì)的分子,。在2008年7月11日出版的《細(xì)胞》(Cell)上,來自美國加州大學(xué)伯克利分校的Campellone等發(fā)表了他們的最新研究結(jié)果,,文章表示,,他們發(fā)現(xiàn)了一種被稱為WHAMM的蛋白,其名稱是“肌動蛋白,、細(xì)胞膜,、微管相關(guān)WASP同源體”(WASP homolog associated with actin, membranes, and microtubules)的縮寫。WHAMM是一種肌動蛋白核化Arp2/3復(fù)合物的催化劑,該復(fù)合物能與高爾基膜(Golgi membranes)以及微管發(fā)生相互作用,。
微絲相關(guān)蛋白Arp2/3復(fù)合物是一種肌動蛋白成核物質(zhì),,它在很多細(xì)胞生理過程中發(fā)揮著重要作用。而Arp2/3的活性受到成核促進(jìn)因子(nucleation-promoting factors NPFs)的調(diào)節(jié),,NPFs主要在細(xì)胞質(zhì)膜動力過程中起作用,。
科學(xué)家在研究中發(fā)現(xiàn),這種哺乳動物成核促進(jìn)因子WHAMM位于順面高爾基體(cis-Golgi apparatus)以及管泡膜輸運(yùn)中間體等處,。WHAMM的典型結(jié)構(gòu)一般包括一個氨基端域(N-terminal domain),,它負(fù)責(zé)調(diào)節(jié)高爾基膜結(jié)合微管的螺旋狀結(jié)構(gòu),以及一個WCA片段,,該片段主要激發(fā)Arp2/3調(diào)節(jié)的肌動蛋白聚合過程,。過度表達(dá)/抑制實(shí)驗(yàn)顯示,WHAMM對于維持高爾基體的結(jié)構(gòu)以及促進(jìn)順式膜轉(zhuǎn)運(yùn)(蛋白從內(nèi)質(zhì)網(wǎng)沿著高爾基體向質(zhì)膜轉(zhuǎn)運(yùn))非常重要,。此外,,WHAMM與微管發(fā)生相互作用的能力將幫助膜管形成,這是由于其誘導(dǎo)肌動蛋白組裝的能力能促進(jìn)微管生長,。WHAMM對細(xì)胞膜成管作用的促進(jìn)使其在內(nèi)質(zhì)網(wǎng)(endoplasmic reticulum ER)和高爾基網(wǎng)之間的輸運(yùn)過程中充當(dāng)了重要角色,。
以上結(jié)果表明,WHAMM是一種重要的細(xì)胞膜動力學(xué)的調(diào)節(jié)物質(zhì),,其發(fā)揮功能的主要區(qū)域位于微管和肌動蛋白細(xì)胞骨架的界面上,。(生物谷Bioon.com)
生物谷推薦原始出處:
Cell,Vol 134, 148-161, 11 July 2008,,Kenneth G. Campellone, Matthew D. Welch
WHAMM Is an Arp2/3 Complex Activator That Binds Microtubules and Functions in ER to Golgi Transport
Kenneth G. Campellone,1, Neil J. Webb,1 Elizabeth A. Znameroski,1 and Matthew D. Welch1,
1 Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
Corresponding author
Kenneth G. Campellone
[email protected]
Corresponding author
Matthew D. Welch
[email protected]
Summary
The Arp2/3 complex is an actin nucleator that plays a critical role in many cellular processes. Its activities are regulated by nucleation-promoting factors (NPFs) that function primarily during plasma membrane dynamics. Here we identify a mammalian NPF called WHAMM (WASP homolog associated with actin, membranes, and microtubules) that localizes to the cis-Golgi apparatus and tubulo-vesicular membrane transport intermediates. The modular organization of WHAMM includes an N-terminal domain that mediates Golgi membrane association, a coiled-coil region that binds microtubules, and a WCA segment that stimulates Arp2/3-mediated actin polymerization. Overexpression and depletion studies indicate that WHAMM is important for maintaining Golgi structure and facilitating anterograde membrane transport. The ability of WHAMM to interact with microtubules plays a role in membrane tubulation, while its capacity to induce actin assembly promotes tubule elongation. Thus, WHAMM is an important regulator of membrane dynamics functioning at the interface of the microtubule and actin cytoskeletons.