Integrative Parasitology, Center for Infectious Diseases, Heidelberg University Medical School, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
Department of Cellular Biophysics, Max Planck Institute for Medical Research and Laboratory of Biophysical Chemistry, Heidelberg University, Jahnstrasse 29, 69120 Heidelberg, Germany.
J Cell Sci. 2020 Apr 15;134(5):jcs233775. doi: 10.1242/jcs.233775.
During transmission of malaria-causing parasites from mosquito to mammal, sporozoites migrate at high speed within the skin to access the bloodstream and infect the liver. This unusual gliding motility is based on retrograde flow of membrane proteins and highly dynamic actin filaments that provide short tracks for a myosin motor. Using laser tweezers and parasite mutants, we previously suggested that actin filaments form macromolecular complexes with plasma membrane-spanning adhesins to generate force during migration. Mutations in the actin-binding region of profilin, a near ubiquitous actin-binding protein, revealed that loss of actin binding also correlates with loss of force production and motility. Here, we show that different mutations in profilin, that do not affect actin binding , still generate lower force during sporozoite migration. Lower force generation inversely correlates with increased retrograde flow suggesting that, like in mammalian cells, the slow down of flow to generate force is the key underlying principle governing gliding motility.
在疟原虫从蚊子传播到哺乳动物的过程中， 子孢子在皮肤内高速迁移以进入血液并感染肝脏。这种不寻常的滑行运动依赖于膜蛋白的逆行流动和高度动态的肌动蛋白丝，这些肌动蛋白丝为肌球蛋白马达提供了短程轨道。我们之前使用激光镊子和寄生虫突变体表明，肌动蛋白丝与跨膜黏附蛋白形成大分子复合物，在迁移过程中产生力。肌动蛋白结合蛋白 Profilin 中肌动蛋白结合区的突变表明，肌动蛋白结合的丧失也与力的产生和运动的丧失相关。在这里，我们表明 Profilin 中的不同突变，不影响肌动蛋白结合，在子孢子迁移过程中仍然产生较低的力。力的产生降低与逆行流动增加呈反比，这表明，与哺乳动物细胞一样，减慢流动以产生力是控制滑行运动的关键基本原理。
