Kuiper Jan W P, van Horssen Remco, Oerlemans Frank, Peters Wilma, van Dommelen Michiel M T, te Lindert Mariska M, ten Hagen Timo L M, Janssen Edwin, Fransen Jack A M, Wieringa Bé
Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
PLoS One. 2009;4(3):e5030. doi: 10.1371/journal.pone.0005030. Epub 2009 Mar 31.
Creatine Kinases (CK) catalyze the reversible transfer of high-energy phosphate groups between ATP and phosphocreatine, thereby playing a storage and distribution role in cellular energetics. Brain-type CK (CK-B) deficiency is coupled to loss of function in neural cell circuits, altered bone-remodeling by osteoclasts and complement-mediated phagocytotic activity of macrophages, processes sharing dependency on actomyosin dynamics.
METHODOLOGY/PRINCIPAL FINDINGS: Here, we provide evidence for direct coupling between CK-B and actomyosin activities in cortical microdomains of astrocytes and fibroblasts during spreading and migration. CK-B transiently accumulates in membrane ruffles and ablation of CK-B activity affects spreading and migration performance. Complementation experiments in CK-B-deficient fibroblasts, using new strategies to force protein relocalization from cytosol to cortical sites at membranes, confirmed the contribution of compartmentalized CK-B to cell morphogenetic dynamics.
CONCLUSION/SIGNIFICANCE: Our results provide evidence that local cytoskeletal dynamics during cell motility is coupled to on-site availability of ATP generated by CK-B.
肌酸激酶（CK）催化高能磷酸基团在ATP和磷酸肌酸之间的可逆转移，从而在细胞能量学中发挥储存和分配作用。脑型CK（CK-B）缺乏与神经细胞回路功能丧失、破骨细胞对骨重塑的改变以及巨噬细胞的补体介导吞噬活性相关，这些过程都依赖于肌动球蛋白动力学。
方法/主要发现：在此，我们提供证据表明，在星形胶质细胞和成纤维细胞的皮质微区中，在铺展和迁移过程中，CK-B与肌动球蛋白活性直接相关。CK-B短暂积累在膜皱褶中，CK-B活性的缺失会影响铺展和迁移性能。在CK-B缺陷的成纤维细胞中进行的互补实验，采用新策略迫使蛋白质从细胞质重新定位到膜上的皮质位点，证实了区室化的CK-B对细胞形态发生动力学的贡献。
结论/意义：我们的结果提供了证据，表明细胞运动过程中的局部细胞骨架动力学与CK-B产生的ATP的现场可用性相关。
