Brzeska Hanna, Koech Hilary, Pridham Kevin J, Korn Edward D, Titus Margaret A
Laboratory of Cell Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland.
Department of Genetics, Cell Biology and Development, University of Minnesota, Minneapolis, Minnesota.
Cytoskeleton (Hoboken). 2016 Feb;73(2):68-82. doi: 10.1002/cm.21275. Epub 2016 Feb 22.
Class I myosins are widely expressed with roles in endocytosis and cell migration in a variety of cell types. Dictyostelium express multiple myosin Is, including three short-tailed (Myo1A, Myo1E, Myo1F) and three long-tailed (Myo1B, Myo1C, Myo1D). Here we report the molecular basis of the specific localizations of short-tailed Myo1A, Myo1E, and Myo1F compared to our previously determined localization of long-tailed Myo1B. Myo1A and Myo1B have common and unique localizations consistent with the various features of their tail region; specifically the BH sites in their tails are required for their association with the plasma membrane and heads are sufficient for relocalization to the front of polarized cells. Myo1A does not localize to actin waves and macropinocytic protrusions, in agreement with the absence of a tail region which is required for these localizations of Myo1B. However, in spite of the overall similarity of their domain structures, the cellular distributions of Myo1E and Myo1F are quite different from Myo1A. Myo1E and Myo1F, but not Myo1A, are associated with macropinocytic cups and actin waves. The localizations of Myo1E and Myo1F in macropinocytic structures and actin waves differ from the localization of Myo1B. Myo1B colocalizes with F-actin in the actin waves and at the tips of mature macropinocytic cups whereas Myo1E and Myo1F are in the interior of actin waves and along the entire surface of macropinocytic cups. Our results point to different mechanisms of targeting of short- and long-tailed myosin Is, and are consistent with these myosins having both shared and divergent cellular functions.
I类肌球蛋白广泛表达，在多种细胞类型的内吞作用和细胞迁移中发挥作用。盘基网柄菌表达多种肌球蛋白I，包括三种短尾型（肌球蛋白1A、肌球蛋白1E、肌球蛋白1F）和三种长尾型（肌球蛋白1B、肌球蛋白1C、肌球蛋白1D）。在此，我们报告了短尾型肌球蛋白1A、肌球蛋白1E和肌球蛋白1F特定定位的分子基础，并与我们之前确定的长尾型肌球蛋白1B的定位进行比较。肌球蛋白1A和肌球蛋白1B具有共同和独特的定位，这与其尾部区域的各种特征一致；具体而言，其尾部的BH位点是它们与质膜结合所必需的，而头部足以使其重新定位到极化细胞的前端。肌球蛋白1A不定位到肌动蛋白波和巨胞饮突起，这与肌球蛋白1B这些定位所需的尾部区域缺失一致。然而，尽管它们的结构域结构总体相似，但肌球蛋白1E和肌球蛋白1F的细胞分布与肌球蛋白1A有很大不同。肌球蛋白1E和肌球蛋白1F，而非肌球蛋白1A，与巨胞饮杯和肌动蛋白波相关。肌球蛋白1E和肌球蛋白1F在巨胞饮结构和肌动蛋白波中的定位与肌球蛋白1B的定位不同。肌球蛋白1B在肌动蛋白波和成熟巨胞饮杯的尖端与F-肌动蛋白共定位，而肌球蛋白1E和肌球蛋白1F位于肌动蛋白波内部和巨胞饮杯的整个表面。我们的结果表明短尾型和长尾型肌球蛋白I的靶向机制不同，并且与这些肌球蛋白具有共同和不同的细胞功能一致。
