The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration.
The adenomatous polyposis coli tumor suppressor protein localizes to plasma membrane sites involved in active cell migration.
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DOI：
10.1083/jcb.134.1.165
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发表时间：
1996-07
期刊：
影响因子：
--
通讯作者：
Nelson WJ
中科院分区：
文献类型：
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作者：
Näthke IS;Adams CL;Polakis P;Sellin JH;Nelson WJ
腺瘤性大肠息肉病（APC）基因突变与家族性和散发性结肠癌的息肉形成有关，但该蛋白的功能尚不清楚。我们发现APC蛋白主要定位于微管末端附近的点簇，这些点簇延伸到上皮细胞膜的主动迁移区域。APC蛋白的亚细胞分布需要微管，而不需要肌动蛋白丝。含APC蛋白的膜积极参与细胞迁移，以响应损伤上皮单层，加入原肝细胞生长因子，并在细胞-细胞接触的形成过程中。在肠道中，APC蛋白水平在隐窝/绒毛边界处增加，细胞迁移对于肠细胞从隐窝中退出至关重要，并且细胞在息肉形成过程中积聚，这与APC蛋白微管结合结构域的突变有关。总之，这些数据表明APC蛋白在定向细胞迁移中起作用。
Mutations in the adenomatous polyposis coli (APC) gene are linked to polyp formation in familial and sporadic colon cancer, but the functions of the protein are not known. We show that APC protein localizes mainly to clusters of puncta near the ends of microtubules that extend into actively migrating regions of epithelial cell membranes. This subcellular distribution of APC protein requires microtubules, but not actin filaments. APC protein-containing membranes are actively involved in cell migration in response to wounding epithelial monolayers, addition of the motorgen hepatocyte growth factor, and during the formation of cell-cell contacts. In the intestine, APC protein levels increase at the crypt/villus boundary, where cell migration is crucial for enterocyte exit from the crypt and where cells accumulate during polyp formation that is linked to mutations in the microtubule-binding domain of APC protein. Together, these data indicate that APC protein has a role in directed cell migration.