Structural highlights
Function
[MICA1_HUMAN] Monooxygenase that promotes depolymerization of F-actin by mediating oxidation of specific methionine residues on actin. Acts by modifying actin subunits through the addition of oxygen to form methionine-sulfoxide, leading to promote actin filament severing and prevent repolymerization (Probable). Acts as a cytoskeletal regulator that connects NEDD9 to intermediate filaments. Also acts as a negative regulator of apoptosis via its interaction with STK38 and STK38L; acts by antagonizing STK38 and STK38L activation by MST1/STK4.[1] [2]
Publication Abstract from PubMed
Cytokinetic abscission, the terminal step of cell division, crucially depends on the local constriction of ESCRT-III helices after cytoskeleton disassembly. While the microtubules of the intercellular bridge are cut by the ESCRT-associated enzyme Spastin, the mechanism that clears F-actin at the abscission site is unknown. Here we show that oxidation-mediated depolymerization of actin by the redox enzyme MICAL1 is key for ESCRT-III recruitment and successful abscission. MICAL1 is recruited to the abscission site by the Rab35 GTPase through a direct interaction with a flat three-helix domain found in MICAL1 C terminus. Mechanistically, in vitro assays on single actin filaments demonstrate that MICAL1 is activated by Rab35. Moreover, in our experimental conditions, MICAL1 does not act as a severing enzyme, as initially thought, but instead induces F-actin depolymerization from both ends. Our work reveals an unexpected role for oxidoreduction in triggering local actin depolymerization to control a fundamental step of cell division.
Oxidation of F-actin controls the terminal steps of cytokinesis.,Fremont S, Hammich H, Bai J, Wioland H, Klinkert K, Rocancourt M, Kikuti C, Stroebel D, Romet-Lemonne G, Pylypenko O, Houdusse A, Echard A Nat Commun. 2017 Feb 23;8:14528. doi: 10.1038/ncomms14528. PMID:28230050[3]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Schmidt EF, Shim SO, Strittmatter SM. Release of MICAL autoinhibition by semaphorin-plexin signaling promotes interaction with collapsin response mediator protein. J Neurosci. 2008 Feb 27;28(9):2287-97. doi: 10.1523/JNEUROSCI.5646-07.2008. PMID:18305261 doi:http://dx.doi.org/10.1523/JNEUROSCI.5646-07.2008
- ↑ Zucchini D, Caprini G, Pasterkamp RJ, Tedeschi G, Vanoni MA. Kinetic and spectroscopic characterization of the putative monooxygenase domain of human MICAL-1. Arch Biochem Biophys. 2011 Nov;515(1-2):1-13. doi: 10.1016/j.abb.2011.08.004., Epub 2011 Aug 16. PMID:21864500 doi:http://dx.doi.org/10.1016/j.abb.2011.08.004
- ↑ Fremont S, Hammich H, Bai J, Wioland H, Klinkert K, Rocancourt M, Kikuti C, Stroebel D, Romet-Lemonne G, Pylypenko O, Houdusse A, Echard A. Oxidation of F-actin controls the terminal steps of cytokinesis. Nat Commun. 2017 Feb 23;8:14528. doi: 10.1038/ncomms14528. PMID:28230050 doi:http://dx.doi.org/10.1038/ncomms14528
