Ortegón Salas, Clara
[Author]
;
Helm, Christiane A.
[Degree supervisor];
Lillig, Christopher Horst
[Degree supervisor];
Dick, Tobias P.
[Degree supervisor];
Riemer, Jan
[Degree supervisor]Universität Greifswald
Receptor-induced redox relay reactions control cytoskeletal dynamics
University thesis:
Dissertation, Mathematisch-Naturwissenschaftliche Fakultät der Universität Greifswald, 2021
Footnote:
Literaturverzeichnis: Seite 22-35
Description:
CRMP2, MICAL, redox relay
Survival, development, and function of cells depend on numerous signaling pathways orchestrating the response to external and internal stimuli. Besides the well-established signaling through reversible phosphorylation, the concept of specific, spatio-temporal redox modifications of protein cysteinyl and methionyl side chains that regulate the biological function of these proteins is supported by an overwhelming amount of data. Although the specific reduction of protein redox modifications has been studied intensively, the oxidation of protein side chains was thought to be a result of so-called ‘oxidative stress’. However, this term has been increasingly challenged, since signaling pathways depend on specific, spatio-temporal oxidation of target proteins, most likely catalyzed by specific enzymes. The discovery of MICAL (molecule interacting with CasL) proteins evinced the first examples of specific oxidases in signal transduction in the redox regulation of cellular functions.As part of the semaphorin signaling pathway, MICAL proteins were characterized to stereospecifically oxidize methionyl residues in actin, thereby regulating actin deolymerization, a process important in neurogenesis and cell migration. This oxidation can be reversed by the specific methionine-R-sulfoxide eductase B1. Besides the regulation of actin dynamics, MICALs are involved in the regulation of cell proliferation and apoptosis, and the production of hydrogen peroxide may qualify them as specific oxidases also for cysteinyl residues.