Local ATP generation by brain-type creatine kinase (CK-B) facilitates cell motility

• Published in: PloS one Vol. 4; no. 3; p. e5030
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.03.2009; Public Library of Science (PLoS)
• Subjects: Actomyosin; Actomyosin - metabolism; Adenosine Triphosphate - biosynthesis; Animals; Astrocytes; Astrocytes - ultrastructure; ATP; Biocompatibility; Biology; Biomedical materials; Bone remodeling; Brain; Cell adhesion & migration; Cell Biology/Cell Adhesion; Cell Biology/Cytoskeleton; Cell Biology/Neuronal and Glial Cell Biology; Cell Movement; Complement system; Complementation; Creatine; Creatine kinase; Creatine Kinase, BB Form - metabolism; Creatine Kinase, BB Form - physiology; Cytoskeleton; Cytoskeleton - metabolism; Cytosol; Dehydrogenases; Drosophila; Energy Metabolism; Energy storage; Enzymes; Fibroblasts; Fibroblasts - ultrastructure; Insects; Kinases; Laboratories; Leukocyte migration; Life sciences; Localization; Lymphocytes B; Macrophages; Membrane Microdomains - metabolism; Membranes; Metastasis; Mice; Morphology; Motility; Muscle function; Osteoclasts; Phosphates; Phosphocreatine; Proteins; Spreading
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0005030

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. 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. Our results provide evidence that local cytoskeletal dynamics during cell motility is coupled to on-site availability of ATP generated by CK-B.