Localization of Kif1c mRNA to cell protrusions dictates binding partner specificity of the encoded protein.
Localization of Kif1c mRNA to cell protrusions dictates binding partner specificity of the encoded protein.
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DOI：
10.1101/gad.350320.122
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发表时间：
2023-03-01
影响因子：
10.5
通讯作者：
Mendell, Joshua T.
中科院分区：
文献类型：
--
作者：
Norris, Megan L.;Mendell, Joshua T.
关键词：
在这项研究中，诺里斯（Norris）和门德尔（Mendell）试图了解在细胞迁移过程中，信使核糖核酸（mRNA）定位调控非神经元细胞中蛋白质功能的机制。他们研究了编码驱动蛋白1C（KIF1C）的mRNA定位的功能影响，KIF1C是一种细胞迁移和mRNA运输所必需的驱动蛋白，并且发现Kif1c mRNA定位并不调控KIF1C的蛋白质丰度、分布或运输其他mRNA的能力，还深入了解了mRNA定位到细胞突起与蛋白质 - 蛋白质相互作用特异性之间的机制联系。
信使核糖核酸（mRNA）的亚细胞定位是一种普遍现象，它会影响编码蛋白质的调控和功能。在非神经元细胞中，特定的mRNA定位到细胞突起，并且适当的mRNA定位是细胞迁移所必需的。然而，在这种情况下，mRNA定位调控蛋白质功能的机制仍不清楚。在此，我们研究了编码KIF1C的mRNA定位的功能影响。KIF1C是一种细胞迁移和mRNA运输（包括其自身mRNA的运输）所必需的驱动蛋白。我们发现Kif1c mRNA定位并不调控KIF1C的蛋白质丰度、分布或运输其他mRNA的能力。相反，Kif1c mRNA定位到突起对于定向细胞迁移是必需的。我们使用质谱分析法鉴定内源性KIF1C的结合伴侣，结果显示，由于Kif1c mRNA错误定位，KIF1C相互作用分子的数量和特性发生了显著失调。因此，这些结果揭示了mRNA定位到细胞突起与蛋白质 - 蛋白质相互作用特异性之间的机制联系。我们预计这种机制不限于Kif1c，很可能是一个普遍原则，影响非神经元细胞中富集于突起的mRNA所编码蛋白质的功能。
In this study, Norris and Mendell sought to understand the mechanisms by which mRNA localization regulates protein function in nonneuronal cells during cell migration. They examined the functional consequences of localization of the mRNA encoding KIF1C, a kinesin motor protein required for cell migration and mRNA trafficking, and show that Kif1c mRNA localization does not regulate KIF1C's protein abundance, distribution, or ability to traffic other mRNAs and provide insight into a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein–protein interactions. Subcellular localization of messenger RNA (mRNA) is a widespread phenomenon that can impact the regulation and function of the encoded protein. In nonneuronal cells, specific mRNAs localize to cell protrusions, and proper mRNA localization is required for cell migration. However, the mechanisms by which mRNA localization regulates protein function in this setting remain unclear. Here, we examined the functional consequences of localization of the mRNA encoding KIF1C. KIF1C is a kinesin motor protein required for cell migration and mRNA trafficking, including trafficking of its own mRNA. We show that Kif1c mRNA localization does not regulate KIF1C's protein abundance, distribution, or ability to traffic other mRNAs. Conversely, Kif1c mRNA localization to protrusions is required for directed cell migration. We used mass spectrometry to identify binding partners of endogenous KIF1C, which revealed dramatic dysregulation of the number and identity of KIF1C interactors in response to Kif1c mRNA mislocalization. These results therefore uncovered a mechanistic connection between mRNA localization to cell protrusions and the specificity of protein–protein interactions. We anticipate that this mechanism is not limited to Kif1c and is likely to be a general principle that impacts the functions of proteins encoded by protrusion-enriched mRNAs in nonneuronal cells.
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