Human cryptochrome-1 confers light independent biological activity in transgenic drosophila correlated with flavin radical stability

Jacqueline Vieira, Alex R. Jones, Antoine Danon, Michiyo Sakuma, Nathalie Hoang, David Robles, Shirley Tait, Derren J. Heyes, Marie Picot, Taishi Yoshii, Charlotte Helfrich-Förster, Guillaume Soubigou, Jean Yves Coppee, André Klarsfeld, Francois Rouyer, Nigel S. Scrutton, Margaret Ahmad

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23 Citations (Scopus)

Abstract

Cryptochromes are conserved flavoprotein receptors found throughout the biological kingdom with diversified roles in plant development and entrainment of the circadian clock in animals. Light perception is proposed to occur through flavin radical formation that correlates with biological activity in vivo in both plants and Drosophila. By contrast, mammalian (Type II) cryptochromes regulate the circadian clock independently of light, raising the fundamental question of whether mammalian cryptochromes have evolved entirely distinct signaling mechanisms. Here we show by developmental and transcriptome analysis that Homo sapiens cryptochrome - 1 (HsCRY1) confers biological activity in transgenic expressing Drosophila in darkness, that can in some cases be further stimulated by light. In contrast to all other cryptochromes, purified recombinant HsCRY1 protein was stably isolated in the anionic radical flavin state, containing only a small proportion of oxidized flavin which could be reduced by illumination. We conclude that animal Type I and Type II cryptochromes may both have signaling mechanisms involving formation of a flavin radical signaling state, and that light independent activity of Type II cryptochromes is a consequence of dark accumulation of this redox form in vivo rather than of a fundamental difference in signaling mechanism.

Original languageEnglish
Article numbere31867
JournalPloS one
Volume7
Issue number3
DOIs
Publication statusPublished - Mar 12 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Vieira, J., Jones, A. R., Danon, A., Sakuma, M., Hoang, N., Robles, D., Tait, S., Heyes, D. J., Picot, M., Yoshii, T., Helfrich-Förster, C., Soubigou, G., Coppee, J. Y., Klarsfeld, A., Rouyer, F., Scrutton, N. S., & Ahmad, M. (2012). Human cryptochrome-1 confers light independent biological activity in transgenic drosophila correlated with flavin radical stability. PloS one, 7(3), [e31867]. https://doi.org/10.1371/journal.pone.0031867