Mical links semaphorins to F-actin disassembly

Ruei Jiun Hung, Umar Yazdani, Jimok Yoon, Heng Wu, Taehong Yang, Nidhi Gupta, Zhiyu Huang, Willem J H Van Berkel, Jonathan R. Terman

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

How instructive cues present on the cell surface have their precise effects on the actin cytoskeleton is poorly understood. Semaphorins are one of the largest families of these instructive cues and are widely studied for their effects on cell movement, navigation, angiogenesis, immunology and cancer. Semaphorins/collapsins were characterized in part on the basis of their ability to drastically alter actin cytoskeletal dynamics in neuronal processes, but despite considerable progress in the identification of semaphorin receptors and their signalling pathways, the molecules linking them to the precise control of cytoskeletal elements remain unknown. Recently, highly unusual proteins of the Mical family of enzymes have been found to associate with the cytoplasmic portion of plexins, which are large cell-surface semaphorin receptors, and to mediate axon guidance, synaptogenesis, dendritic pruning and other cell morphological changes. Mical enzymes perform reduction-oxidation (redox) enzymatic reactions and also contain domains found in proteins that regulate cell morphology. However, nothing is known of the role of Mical or its redox activity in mediating morphological changes. Here we report that Mical directly links semaphorins and their plexin receptors to the precise control of actin filament (F-actin) dynamics. We found that Mical is both necessary and sufficient for semaphorin-plexin-mediated F-actin reorganization in vivo. Likewise, we purified Mical protein and found that it directly binds F-actin and disassembles both individual and bundled actin filaments. We also found that Mical utilizes its redox activity to alter F-actin dynamics in vivo and in vitro, indicating a previously unknown role for specific redox signalling events in actin cytoskeletal regulation. Mical therefore is a novel F-actin-disassembly factor that provides a molecular conduit through which actin reorganizationa hallmark of cell morphological changes including axon navigationcan be precisely achieved spatiotemporally in response to semaphorins.

Original languageEnglish (US)
Pages (from-to)823-827
Number of pages5
JournalNature
Volume463
Issue number7282
DOIs
StatePublished - Feb 11 2010

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Semaphorins
Actins
Actin Cytoskeleton
Cues
Semaphorin-3A
Proteins
Neuronal Plasticity
Aptitude
Cell Surface Receptors
Enzymes
Allergy and Immunology
Cell Movement
Axons

ASJC Scopus subject areas

  • General

Cite this

Hung, R. J., Yazdani, U., Yoon, J., Wu, H., Yang, T., Gupta, N., ... Terman, J. R. (2010). Mical links semaphorins to F-actin disassembly. Nature, 463(7282), 823-827. https://doi.org/10.1038/nature08724

Mical links semaphorins to F-actin disassembly. / Hung, Ruei Jiun; Yazdani, Umar; Yoon, Jimok; Wu, Heng; Yang, Taehong; Gupta, Nidhi; Huang, Zhiyu; Van Berkel, Willem J H; Terman, Jonathan R.

In: Nature, Vol. 463, No. 7282, 11.02.2010, p. 823-827.

Research output: Contribution to journalArticle

Hung, RJ, Yazdani, U, Yoon, J, Wu, H, Yang, T, Gupta, N, Huang, Z, Van Berkel, WJH & Terman, JR 2010, 'Mical links semaphorins to F-actin disassembly', Nature, vol. 463, no. 7282, pp. 823-827. https://doi.org/10.1038/nature08724
Hung RJ, Yazdani U, Yoon J, Wu H, Yang T, Gupta N et al. Mical links semaphorins to F-actin disassembly. Nature. 2010 Feb 11;463(7282):823-827. https://doi.org/10.1038/nature08724
Hung, Ruei Jiun ; Yazdani, Umar ; Yoon, Jimok ; Wu, Heng ; Yang, Taehong ; Gupta, Nidhi ; Huang, Zhiyu ; Van Berkel, Willem J H ; Terman, Jonathan R. / Mical links semaphorins to F-actin disassembly. In: Nature. 2010 ; Vol. 463, No. 7282. pp. 823-827.
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