The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from Drosophila to Humans

Heng Wu, Hunkar Gizem Yesilyurt, Jimok Yoon, Jonathan R. Terman

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

Cellular form and function - and thus normal development and physiology - are specified via proteins that control the organization and dynamic properties of the actin cytoskeleton. Using the Drosophila model, we have recently identified an unusual actin regulatory enzyme, Mical, which is directly activated by F-actin to selectively post-translationally oxidize and destabilize filaments - regulating numerous cellular behaviors. Mical proteins are also present in mammals, but their actin regulatory properties, including comparisons among different family members, remain poorly defined. We now find that each human MICAL family member, MICAL-1, MICAL-2, and MICAL-3, directly induces F-actin dismantling and controls F-actin-mediated cellular remodeling. Specifically, each human MICAL selectively associates with F-actin, which directly induces MICALs catalytic activity. We also find that each human MICAL uses an NADPH-dependent Redox activity to post-translationally oxidize actin's methionine (M) M44/M47 residues, directly dismantling filaments and limiting new polymerization. Genetic experiments also demonstrate that each human MICAL drives F-actin disassembly in vivo, reshaping cells and their membranous extensions. Our results go on to reveal that MsrB/SelR reductase enzymes counteract each MICAL's effect on F-actin in vitro and in vivo. Collectively, our results therefore define the MICALs as an important phylogenetically-conserved family of catalytically-acting F-actin disassembly factors.

Original languageEnglish (US)
Article number17943
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

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Drosophila
Actins
Oxidoreductases
Enzymes
Actin Cytoskeleton
NADP
Polymerization
Methionine
Oxidation-Reduction
Mammals
Proteins
Organizations

ASJC Scopus subject areas

  • General

Cite this

The MICALs are a Family of F-actin Dismantling Oxidoreductases Conserved from Drosophila to Humans. / Wu, Heng; Yesilyurt, Hunkar Gizem; Yoon, Jimok; Terman, Jonathan R.

In: Scientific Reports, Vol. 8, No. 1, 17943, 01.12.2018.

Research output: Contribution to journalArticle

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