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


RESULTS
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.


CONCLUSIONS
Our results provide evidence that local cytoskeletal dynamics during cell motility is coupled to on-site availability of ATP generated by CK-B.
Kuiper
Jan W P
JW
Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences (NCMLS), Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
van Horssen
Remco
R
Oerlemans
Frank
F
Peters
Wilma
W
van Dommelen
Michiel M T
MM
te Lindert
Mariska M
MM
ten Hagen
Timo L M
TL
Janssen
Edwin
E
Fransen
Jack A M
JA
Wieringa
Bé
B