...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Oncogene >The NF2 tumor suppressor regulates microtubule-based vesicle trafficking via a novel Rac, MLK and p38SAPK pathway
【24h】

The NF2 tumor suppressor regulates microtubule-based vesicle trafficking via a novel Rac, MLK and p38SAPK pathway

机译：NF2肿瘤抑制剂通过新的RAC，MLK和P38SAPK途径调节基于微管的囊泡贩运

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Neurofibromatosis type 2 patients develop schwannomas, meningiomas and ependymomas resulting from mutations in the tumor suppressor gene, NF2, encoding a membrane-cytoskeleton adapter protein called merlin. Merlin regulates contact inhibition of growth and controls the availability of growth factor receptors at the cell surface. We tested if microtubule-based vesicular trafficking might be a mechanism by which merlin acts. We found that schwannoma cells, containing merlin mutations and constitutive activation of the Rho/Rac family of GTPases, had decreased intracellular vesicular trafficking relative to normal human Schwann cells. In Nf2?/? mouse Schwann (SC4) cells, re-expression of merlin as well as inhibition of Rac or its effector kinases, MLK and p38SAPK, each increased the velocity of Rab6 positive exocytic vesicles. Conversely, an activated Rac mutant decreased Rab6 vesicle velocity. Vesicle motility assays in isolated squid axoplasm further demonstrated that both mutant merlin and active Rac specifically reduce anterograde microtubule-based transport of vesicles dependent upon the activity of p38SAPK kinase. Taken together, our data suggest loss of merlin results in the Rac-dependent decrease of anterograde trafficking of exocytic vesicles, representing a possible mechanism controlling the concentration of growth factor receptors at the cell surface.
机译：神经纤维瘤病2患者开发施瓦马苗族，脑膜瘤和突出血瘤，由肿瘤抑制基因NF2中的突变，编码致称为MERLIN的膜 - 细胞骨架适配器蛋白。 Merlin调节了生长的接触抑制，并控制细胞表面上生长因子受体的可用性。我们测试了基于微管的肤色贩运可能是Merlin作用的机制。我们发现，含有Merlin突变和GTP酶系列的rho / Rac系列的组成型激活的Schwannoma细胞已经降低了相对于正常人施曼细胞的细胞内覆膜。在NF2？/？ Mouse Schwann（SC4）细胞，重新表达Merlin以及RAC或其效应激酶，MLK和P38SAPK的抑制，每次增加RAB6阳性外血囊泡的速度。相反，活化的RAC突变体减少了RAB6囊泡速度。孤立的鱿鱼桥中的囊泡运动性测定进一步证明了突变体Merlin和活性RAC依赖于P38SAPK激酶的活性，特别降低基于囊泡的囊泡的囊性。我们的数据建议我们的数据表明Merlin的丧失导致对非血细胞囊泡的Anterograde种贩的Rac依赖性降低，代表了控制细胞表面上生长因子受体浓度的可能机制。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号