Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration in MDCK cells
Over-expression of PAR-3 suppresses contact-mediated inhibition of cell migration in MDCK cells
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DOI：
10.1046/j.1365-2443.2002.00540.x
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发表时间：
2002-06-01
期刊：
影响因子：
2.1
通讯作者：
Ohno, S
中科院分区：
文献类型：
--
作者：
Mishima, A;Suzuki, A;Ohno, S
背景资料：PAR-3是PAR蛋白中的一种，以前称为ASIP，其对于胚胎以及分化的上皮细胞中细胞极性的建立是必不可少的。在哺乳动物上皮细胞中，它与aPKC和PAR-6形成三元复合物，并定位于紧密连接，已被建议为重要的创建cell polarity.Results：为了深入了解PAR-3在哺乳动物上皮细胞中的功能模式，我们研究了PAR-3过表达在MDCK细胞中的效果。虽然外源性PAR-3-表达不影响汇合细胞的上皮极性，但它将低密度细胞的形态急剧转变为具有发达膜突起的成纤维细胞形式。延时观察显示，PAR-3过表达的细胞显示出强烈的运动性，即使在它们组装成松散的集落后，这表明接触介导的细胞迁移抑制（CIM）受到抑制。E-cadherin和vimentin的表达不随PAR-3的过度表达而改变，表明外源性PAR-3仅干扰基本成纤维细胞结构和上皮结构之间的细胞状态的内源性平衡。显性负突变体的Rac 1和另外的诺考达唑的共同表达强烈拮抗PAR-3过表达的效果，表明参与Rac 1激活和微管polymerizations.Conclusions：这里提出的数据表明一个有趣的联系之间的接触介导的抑制细胞迁移和调节细胞极性。假定PAR-3的活动，这里证明可能是内源性的上皮细胞极化过程中被隔离从胞质到细胞-细胞连接区与aPKC和PAR-6后，细胞-细胞粘附。
Background: PAR-3 is one of the PAR proteins, previously named ASIP which are indispensable for the establishment of cell polarity in the embryo as well as differentiated epithelial cells. In mammalian epithelial cells, it forms a ternary complex with aPKC and PAR-6, and is localized to the tight junction that has been suggested as being important for creating cell polarity.Results: To gain insights into the mode of PAR-3 function in mammalian epithelial cells, we examined the effect of PAR-3 over-expression in MDCK cells. Although exogenous PAR-3-expression does not affect the epithelial polarity of confluent cells, it drastically transforms the morphology of cells at low density into a fibroblastic form with developed membrane protrusions. Time-lapse observations have revealed that PAR-3 over-expressing cells show intense motility, even after they have assembled into loose colonies, suggesting that the contact-mediated inhibition of cell migration (CIM) is suppressed. The expressions of E-cadherin and vimentin do not change with PAR-3 over-expression, suggesting that exogenous PAR-3 only disturbs the endogenous equilibrium of cellular states between a fundamental fibroblastic structure and an epithelial one. The co-expression of a dominant negative mutant of Rac1 and the addition of nocodazole strongly antagonize the effect of PAR-3 over-expression, suggesting the involvement of Rac1 activation and microtubule polymerizations.Conclusions: The data presented here suggest an intriguing link between the contact-mediated inhibition of cell migration and the regulation of cell polarity. The putative PAR-3 activities demonstrated here may function endogenously in the epithelial cell polarization process by being sequestered from the cytosol to the cell-cell junctional regions with aPKC and PAR-6 upon cell-cell adhesion.