1. Differential regulation of actin microfilaments by human MICAL proteins.
- Author
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Giridharan SS, Rohn JL, Naslavsky N, and Caplan S
- Subjects
- Actin Cytoskeleton chemistry, Adaptor Proteins, Signal Transducing antagonists & inhibitors, Adaptor Proteins, Signal Transducing chemistry, Adaptor Proteins, Signal Transducing genetics, Animals, Axons metabolism, Base Sequence, Cell Adhesion Molecules metabolism, Cell Line, Cytoskeletal Proteins antagonists & inhibitors, Cytoskeletal Proteins chemistry, Cytoskeletal Proteins genetics, DNA Primers genetics, DNA-Binding Proteins metabolism, HeLa Cells, Humans, LIM Domain Proteins antagonists & inhibitors, LIM Domain Proteins chemistry, LIM Domain Proteins genetics, Microfilament Proteins antagonists & inhibitors, Microfilament Proteins chemistry, Microfilament Proteins genetics, Mixed Function Oxygenases, Nerve Tissue Proteins metabolism, Oxidoreductases antagonists & inhibitors, Oxidoreductases chemistry, Oxidoreductases genetics, Protein Interaction Domains and Motifs, RNA, Small Interfering genetics, Reactive Oxygen Species metabolism, Semaphorins metabolism, Signal Transduction, Actin Cytoskeleton metabolism, Adaptor Proteins, Signal Transducing metabolism, Cytoskeletal Proteins metabolism, LIM Domain Proteins metabolism, Microfilament Proteins metabolism, Oxidoreductases metabolism
- Abstract
The Drosophila melanogaster MICAL protein is essential for the neuronal growth cone machinery that functions through plexin- and semaphorin-mediated axonal signaling. Drosophila MICAL is also involved in regulating myofilament organization and synaptic structures, and serves as an actin disassembly factor downstream of plexin-mediated axonal repulsion. In mammalian cells there are three known isoforms, MICAL1, MICAL2 and MICAL3, as well as the MICAL-like proteins MICAL-L1 and MICAL-L2, but little is known of their function, and information comes almost exclusively from neural cells. In this study we show that in non-neural cells human MICALs are required for normal actin organization, and all three MICALs regulate actin stress fibers. Moreover, we provide evidence that the generation of reactive oxygen species by MICAL proteins is crucial for their actin-regulatory function. However, although MICAL1 is auto-inhibited by its C-terminal coiled-coil region, MICAL2 remains constitutively active and affects stress fibers. These data suggest differential but complementary roles for MICAL1 and MICAL2 in actin microfilament regulation.
- Published
- 2012
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