[F-actin]-monooxygenase MICAL1

MICAL1 is a monooxygenase that catalyzes oxidation of F-actin methionine residues, promoting actin filament depolymerization and preventing repolymerization (UniProt: Q8TDZ2). In the absence of actin, it functions as a NADPH oxidase producing hydrogen peroxide. The protein acts as a cytoskeletal regulator connecting NEDD9 to intermediate filaments and negatively regulates apoptosis through interactions with STK38 and STK38L kinases.

MICAL1 is involved in nervous system development, particularly in regulating lamina-specific hippocampal connectivity through redox regulation of the actin cytoskeleton (UniProt: Q8TDZ2). It controls intracellular distribution of secretory vesicles containing neuronal adhesion molecules and participates in endosomal tubule extension via interaction with RAB8, RAB10, and GRAF proteins, thereby regulating protein export.

MICAL1 is down-regulated in Alzheimer's disease brain tissue (Chaparral AD proteomics; mean log2FC: −0.38), suggesting reduced actin dynamics and potential cytoskeletal dysfunction in AD pathology. This decrease may impair synaptic connectivity and vesicle trafficking processes critical for neuronal function.