Local ATP generation by brain-type creatine kinase (CK-B) facilities cell motility
Background: 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.
|Persistent URL||dx.doi.org/10.1371/journal.pone.0005030, hdl.handle.net/1765/24982|
Kuiper, J.W.P., van Horssen, R., Oerlemans, F., Peters, W., van Dommelen, M.M.T., te Lindert, M.M., … Wieringa, B.. (2009). Local ATP generation by brain-type creatine kinase (CK-B) facilities cell motility. PLoS ONE, 4(3). doi:10.1371/journal.pone.0005030