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MICAL, the Flavoenzyme Participating in Cytoskeleton Dynamics
Department of Biosciences, University of Milan, Via Celoria 26, Milano 20133, Italy
* Author to whom correspondence should be addressed.
Received: 2 November 2012; in revised form: 2 March 2013 / Accepted: 11 March 2013 / Published: 27 March 2013
(This article belongs to the Special Issue Flavins
Abstract: MICAL (from the Molecule Interacting with CasL) indicates a family of recently discovered cytosolic, multidomain proteins, which uniquely couple an N-terminal FAD-containing monooxygenase-like domain to typical calponine homology, LIM and coiled-coil protein-interaction modules. Genetic and cell biology approaches have demonstrated an essential role of the catalytic activity of the monooxygenase-like domain in transducing the signal initiated by semaphorins interaction with their plexin receptors, which results in local actin cytoskeleton disassembly as part of fundamental processes that include differentiation, migration and cell-cell contacts in neuronal and non-neuronal cell types. This review focuses on the structure-function relations of the MICAL monooxygenase-like domain as they are emerging from the available in vitro studies on mouse, human and Drosophila MICAL forms that demonstrated a NADPH-dependent actin depolymerizing activity of MICAL. With Drosophila MICAL forms, actin depolymerization was demonstrated to be associated to conversion of Met44 to methionine sulfone through a postulated hydroxylating reaction. Arguments supporting the concept that MICAL effect on F-actin may be reversible will be discussed.
Keywords: MICAL; flavoprotein; NADPH oxidase; monooxygenase; semaphorin signaling; actin dynamics
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Vanoni, M.A.; Vitali, T.; Zucchini, D. MICAL, the Flavoenzyme Participating in Cytoskeleton Dynamics. Int. J. Mol. Sci. 2013, 14, 6920-6959.
Vanoni MA, Vitali T, Zucchini D. MICAL, the Flavoenzyme Participating in Cytoskeleton Dynamics. International Journal of Molecular Sciences. 2013; 14(4):6920-6959.
Vanoni, Maria A.; Vitali, Teresa; Zucchini, Daniela. 2013. "MICAL, the Flavoenzyme Participating in Cytoskeleton Dynamics." Int. J. Mol. Sci. 14, no. 4: 6920-6959.