The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin.
The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin.
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DOI：
10.1371/journal.pone.0000844
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发表时间：
2007-09-05
期刊：
影响因子：
3.7
通讯作者：
Carducci MA
中科院分区：
文献类型：
--
作者：
Kachhap SK;Faith D;Qian DZ;Shabbeer S;Galloway NL;Pili R;Denmeade SR;DeMarzo AM;Carducci MA
细胞间的黏附是由存在于细胞表面的黏附分子介导的。形成黏附复合体的分子下调是转移性癌细胞的特征。下调N-myc下调基因1(NDRG1)会增加前列腺癌和乳腺癌的转移。NDRG1的确切功能尚不清楚。在这里，通过使用活细胞共聚焦显微镜和体外重建，我们报告了NDRG1参与了黏附分子E-钙粘蛋白的循环，从而稳定了它。有证据表明，NDRG1通过与磷酸肌醇4-磷酸结合，在反高尔基体网络中招募内小体循环，并与膜结合的Rab4aGTP酶相互作用。NDRG1与结构活性的Rab4aQ67L突变蛋白特异性结合，而不与GDP结合的Rab4aS22N突变蛋白结合，证明NDRG1是一种新的Rab4a效应蛋白。转铁蛋白回收实验表明，NDRG1在回收阶段与转铁蛋白共定位。NDRG1改变细胞内转铁蛋白循环的动力学。NDRG1基因敲除细胞表现出转铁蛋白回收的延迟，反之，NDRG1过表达的细胞表现出转铁蛋白回收速率的增加。这一新发现的NDRG1作为一种参与E-钙粘蛋白循环的循环蛋白，将有助于理解NDRG1作为一种转移抑制蛋白的作用。
Cell to cell adhesion is mediated by adhesion molecules present on the cell surface. Downregulation of molecules that form the adhesion complex is a characteristic of metastatic cancer cells. Downregulation of the N-myc down regulated gene1 (NDRG1) increases prostate and breast metastasis. The exact function of NDRG1 is not known. Here by using live cell confocal microscopy and in vitro reconstitution, we report that NDRG1 is involved in recycling the adhesion molecule E-cadherin thereby stabilizing it. Evidence is provided that NDRG1 recruits on recycling endosomes in the Trans Golgi network by binding to phosphotidylinositol 4-phosphate and interacts with membrane bound Rab4aGTPase. NDRG1 specifically interacts with constitutively active Rab4aQ67L mutant protein and not with GDP-bound Rab4aS22N mutant proving NDRG1 as a novel Rab4a effector. Transferrin recycling experiments reveals NDRG1 colocalizes with transferrin during the recycling phase. NDRG1 alters the kinetics of transferrin recycling in cells. NDRG1 knockdown cells show a delay in recycling transferrin, conversely NDRG1 overexpressing cells reveal an increase in rate of transferrin recycling. This novel finding of NDRG1 as a recycling protein involved with recycling of E-cadherin will aid in understanding NDRG1 role as a metastasis suppressor protein.
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影响因子：
5.3
作者：
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作者：
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