Local ATP Generation by Brain-Type Creatine Kinase (CK-B) Facilitates Cell Motility

JWP Kuiper, R van Horssen, F (Frank) Oerlemans, W Peters, MMT van Dommelen, MMT Lindert, Timo ten Hagen, E (Edwin) Janssen, JAM Fransen, B Wieringa

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Abstract

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.
Original languageUndefined/Unknown
JournalPLoS One (print)
Volume4
Issue number3
DOIs
Publication statusPublished - 2009

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