美國葉什瓦大學阿爾伯特愛因斯坦醫(yī)學院的研究人員發(fā)現(xiàn),,劍蛋白酶在調(diào)節(jié)細胞運動方面發(fā)揮著至關重要的作用,這一發(fā)現(xiàn)對治療糖尿病潰瘍以及轉(zhuǎn)移性癌癥具有十分重要的意義,。
細胞運動可以類比于人類的行走過程,反復循環(huán),,其中的每個步驟都受到精巧的調(diào)節(jié)控制,。細胞向前“邁步”主要以形成前端突出進行。細胞運動不僅對于組織器官的生長發(fā)育以及基礎免疫反應和傷口愈合十分關鍵,,同時不受控制的細胞轉(zhuǎn)移也會導致智障,、血管疾病和癌癥轉(zhuǎn)移等災難性疾病。
葉什瓦大學阿爾伯特愛因斯坦醫(yī)學院生理學和生物物理學副教授大衛(wèi)·夏普博士及其同事發(fā)現(xiàn),,一種名為劍蛋白(katanin)酶家族的某些特定酶可動態(tài)調(diào)節(jié)細胞運動,。劍蛋白是一種與微管有關的ATP酶,可使微管斷裂,,并使微管解聚為微管蛋白的二聚體,。它主要集中在非分裂細胞外緣,可控制被稱為偽足的突起,。
當夏普博士領導的研究小組利用可抑制劍蛋白的藥物來處理果蠅的運動細胞時發(fā)現(xiàn),,處理后的細胞的移動速度顯著增加,明顯快于對照細胞,。這表明劍蛋白可控制細胞運動,,并防止細胞移動過快。研究人員在人體細胞中也觀察到了類似的結果,。
夏普博士認為,,劍蛋白可以描述為微管調(diào)節(jié)器,它能夠調(diào)節(jié)細胞運動的速度和方向,。臨床藥物可通過抑制劍蛋白來刺激細胞向某一特定方向遷移,,進而達到治病效果,劍蛋白或可刺激劍蛋白的藥物可能會在治療和預防癌癥轉(zhuǎn)移等方面具有重要價值,。(生物谷Bioon.com)
生物谷推薦原文出處:
Nature Cell Biology doi:10.1038/ncb2206
Drosophila katanin is a microtubule depolymerase that regulates cortical-microtubule plus-end interactions and cell migration
Dong Zhang,1 Kyle D. Grode,2, 5 Shannon F. Stewman,1, 5 Juan Daniel Diaz-Valencia,3, 5 Emily Liebling,1 Uttama Rath,1 Tania Riera,1 Joshua D. Currie,2 Daniel W. Buster,4 Ana B. Asenjo,1 Hernando J. Sosa,1 Jennifer L. Ross,3, 5 Ao Ma,1, 5 Stephen L. Rogers2, 5 & David J. Sharp1
Regulation of microtubule dynamics at the cell cortex is important for cell motility, morphogenesis and division. Here we show that the Drosophila katanin Dm-Kat60 functions to generate a dynamic cortical-microtubule interface in interphase cells. Dm-Kat60 concentrates at the cell cortex of S2 Drosophila cells during interphase, where it suppresses the polymerization of microtubule plus-ends, thereby preventing the formation of aberrantly dense cortical arrays. Dm-Kat60 also localizes at the leading edge of migratory D17 Drosophila cells and negatively regulates multiple parameters of their motility. Finally, in vitro, Dm-Kat60 severs and depolymerizes microtubules from their ends. On the basis of these data, we propose that Dm-Kat60 removes tubulin from microtubule lattice or microtubule ends that contact specific cortical sites to prevent stable and/or lateral attachments. The asymmetric distribution of such an activity could help generate regional variations in microtubule behaviours involved in cell migration.