封面圖片：Yip等人發(fā)現(xiàn)一種非常規(guī)肌漿球蛋白Myo1c會(huì)發(fā)生磷酸化,，并且調(diào)節(jié)GLUT4囊泡的運(yùn)輸,。封面將這一過程描繪為電路，Myo1c是其中的電動(dòng)機(jī)皮帶輪,，它將GLUT4囊泡運(yùn)送到質(zhì)膜,。胰島素能通過依賴于PI3K/Ca2+/ CaMKII的磷酸化增強(qiáng)Myo1c ATP激酶的活性。封面背景綠色部分為脂肪細(xì)胞,。）
在胰島素應(yīng)答組織（insulin-responsive tissue）-包括脂肪和肌肉組織中,，胰島素能激發(fā)一系列的級(jí)聯(lián)反應(yīng)，促使富含葡萄糖轉(zhuǎn)運(yùn)蛋白GLUT4的囊泡向著質(zhì)膜移動(dòng),。GLUT4是一種位于胰島素敏感組織的胞漿,、質(zhì)膜上的糖蛋白，其主要功能是幫助葡萄糖向胞內(nèi)轉(zhuǎn)運(yùn),。沒有發(fā)生胰島素刺激時(shí),，GLUT4主要位于細(xì)胞內(nèi)的儲(chǔ)存囊泡內(nèi)，而當(dāng)囊泡轉(zhuǎn)移到外膜并且彼此融合時(shí),，GLUT4活性增加,，與葡萄糖結(jié)合并發(fā)生結(jié)構(gòu)變化,，葡萄糖被轉(zhuǎn)移到細(xì)胞內(nèi)之后，結(jié)構(gòu)又恢復(fù)原狀,。
當(dāng)體內(nèi)組織的胰島素濃度下降時(shí)GLUT4可以迅速作出反應(yīng),，從而保持體內(nèi)的血糖平衡，因此GLUT4的異常將導(dǎo)致組織利用葡萄糖發(fā)生障礙,，形成2型糖尿病,。在2008年11月5日出版的最新一期《細(xì)胞—代謝》（Cell Metabolism）上，來自澳大利亞和美國的研究小組發(fā)現(xiàn),，作為對(duì)胰島素的應(yīng)答,，一種非常規(guī)肌漿球蛋白Myo1c會(huì)發(fā)生磷酸化，并且調(diào)節(jié)GLUT4囊泡的運(yùn)輸,。
非常規(guī)肌漿球蛋白Myo1c與脂肪細(xì)胞中的GLUT4向質(zhì)膜的轉(zhuǎn)運(yùn)過程有關(guān),。Yip等作者證明Myo1c在S701經(jīng)歷依賴胰島素的磷酸化過程，而這一磷酸化過程還伴隨著增強(qiáng)的14-3-3結(jié)合以及減弱的鈣調(diào)蛋白結(jié)合,。重組鈣調(diào)素依賴性蛋白激酶II（CaMKII）與磷酸化過程有關(guān)，而CaMKIIδ的siRNA敲除能消除胰島素依賴的Myo1c磷酸化,。在CaMKII 磷酸化以及CHO/IR/IRS-1細(xì)胞胰島素刺激之后,，Myo1c的ATP激酶活性會(huì)增加，野生型Myo1c的表達(dá)能恢復(fù)由于siRNA敲除后被阻礙的GLUT4轉(zhuǎn)運(yùn),。
以上的研究結(jié)果表明,，胰島素通過依賴于CaMKII的磷酸化來調(diào)節(jié)Myo1c功能,，而這些功能在胰島素調(diào)節(jié)的脂肪細(xì)胞GLUT4轉(zhuǎn)運(yùn)過程中起到了重要作用,。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell Metabolism,，Volume 8, Issue 5, 384-398, 5 November 2008，Ming Fai Yip, David E. James
CaMKII-Mediated Phosphorylation of the Myosin Motor Myo1c Is Required for Insulin-Stimulated GLUT4 Translocation in Adipocytes
Ming Fai Yip1,Georg Ramm1,Mark Larance1,2,Kyle L. Hoehn1,Mark C. Wagner3,Michael Guilhaus2andDavid E. James1,,
1 Diabetes and Obesity Research Program, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
2 Bioanalytical Mass Spectrometry Facility, University of New South Wales, Sydney, NSW 2052, Australia
3 Department of Medicine, Indiana University School of Medicine, Indianapolis, IN 46202, USA
The unconventional myosin Myo1c has been implicated in insulin-regulated GLUT4 translocation to the plasma membrane in adipocytes. We show that Myo1c undergoes insulin-dependent phosphorylation at S701. Phosphorylation was accompanied by enhanced 14-3-3 binding and reduced calmodulin binding. Recombinant CaMKII phosphorylated Myo1c in vitro and siRNA knockdown of CaMKII abolished insulin-dependent Myo1c phosphorylation in vivo. CaMKII activity was increased upon insulin treatment and the CaMKII inhibitors CN21 and KN-62 or the Ca2+ chelator BAPTA-AM blocked insulin-dependent Myo1c phosphorylation and insulin-stimulated glucose transport in adipocytes. Myo1c ATPase activity was increased after CaMKII phosphorylation in vitro and after insulin stimulation of CHO/IR/IRS-1 cells. Expression of wild-type Myo1c, but not S701A or ATPase dead mutant K111A, rescued the inhibition of GLUT4 translocation by siRNA-mediated Myo1c knockdown. These data suggest that insulin regulates Myo1c function via CaMKII-dependent phosphorylation, and these events play a role in insulin-regulated GLUT4 trafficking in adipocytes likely involving Myo1c motor activity.
