PDF(Pubmed)
Abstract：
Cytoplasmic dynein-1 (dynein) is a microtubule-associated, minus end-directed motor that traffics hundreds of different cargos. Dynein must discriminate between cargos and traffic them at the appropriate time from the correct cellular region. How dynein\'s trafficking activity is regulated in time or cellular space remains poorly understood. Here, we identify CCSer2 as the first known protein to gate dynein activity in the spatial dimension. CCSer2 promotes the migration of developing zebrafish primordium cells and of cultured human cells by facilitating the trafficking of cargos that are acted on by cortically localized dynein. CCSer2 inhibits the interaction between dynein and its regulator Ndel1 exclusively at the cell periphery, resulting in localized dynein activation. Our findings suggest that the spatial specificity of dynein is achieved by the localization of proteins that disinhibit Ndel1. We propose that CCSer2 defines a broader class of proteins that activate dynein in distinct microenvironments via Ndel1 inhibition.
摘要：
胞质动力蛋白-1（动力蛋白）是一种微管相关，负末端定向马达，运输数百种不同的货物。Dynein必须区分货物并在适当的时间从正确的蜂窝区域运输它们。动力蛋白的贩运活动如何在时间或细胞空间中受到调节仍然知之甚少。这里,我们确定CCSer2是第一个在空间维度上门控动力蛋白活性的已知蛋白质。CCSer2促进发育中的斑马鱼原基细胞和培养的人细胞的迁移，通过促进由皮质定位的动力蛋白作用的货物的运输。CCSer2仅在细胞外周抑制动力蛋白与其调节因子Ndel1之间的相互作用，导致局部动力蛋白激活。我们的发现表明，动力蛋白的空间特异性是通过定位抑制Ndel1的蛋白质来实现的。我们建议CCSer2定义了一类更广泛的蛋白质，这些蛋白质通过Ndel1抑制在不同的微环境中激活动力蛋白。
