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.
Highlights
MICAL indicates a family of recently discovered multidomain proteins [1,2], which participate in the control of cytoskeleton dynamics with still poorly understood mechanisms
A peculiar feature of MICAL proteins is the presence of an N-terminal region structurally related to the bacterial FAD-containing aromatic monooxygenases [1,2,3,4] of which p-hydroxybenzoate hydroxylase (PHBH) is the prototype ([5,6] and references therein)
MICALs appear to be unique among proteins involved in cytoskeleton dynamics in that they may establish a direct link between cell oxidoreduction metabolism and cytoskeleton rearrangements, which are at the basis of cell proliferation, migration and differentiation, cell-cell contacts and intracellular vesicle trafficking in health and disease [7]
Summary
MICAL (from the Molecule Interacting with CasL) indicates a family of recently discovered multidomain proteins [1,2], which participate in the control of cytoskeleton dynamics with still poorly understood mechanisms. Most of our knowledge on MICAL function derives from genetic and cell biology studies, which have been presented in several recent reviews [8,9,10,11,12,13,14,15,16], which will be briefly summarized here. Much less is known about the actual structure-function relations of MICALs as derived from in vitro biochemical studies of isolated protein forms, which are the focus of this article
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
