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 language | English |
|---|---|
| Article number | e31867 |
| Journal | PLoS One |
| Volume | 7 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Mar 12 2012 |
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ASJC Scopus subject areas
- Agricultural and Biological Sciences(all)
- Biochemistry, Genetics and Molecular Biology(all)
- Medicine(all)
Cite this
Human cryptochrome-1 confers light independent biological activity in transgenic drosophila correlated with flavin radical stability. / Vieira, Jacqueline; Jones, Alex R.; Danon, Antoine; Sakuma, Michiyo; Hoang, Nathalie; Robles, David; Tait, Shirley; Heyes, Derren J.; Picot, Marie; Yoshii, Taishi; Helfrich-Förster, Charlotte; Soubigou, Guillaume; Coppee, Jean Yves; Klarsfeld, André; Rouyer, Francois; Scrutton, Nigel S.; Ahmad, Margaret.
In: PLoS One, Vol. 7, No. 3, e31867, 12.03.2012.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Human cryptochrome-1 confers light independent biological activity in transgenic drosophila correlated with flavin radical stability
AU - Vieira, Jacqueline
AU - Jones, Alex R.
AU - Danon, Antoine
AU - Sakuma, Michiyo
AU - Hoang, Nathalie
AU - Robles, David
AU - Tait, Shirley
AU - Heyes, Derren J.
AU - Picot, Marie
AU - Yoshii, Taishi
AU - Helfrich-Förster, Charlotte
AU - Soubigou, Guillaume
AU - Coppee, Jean Yves
AU - Klarsfeld, André
AU - Rouyer, Francois
AU - Scrutton, Nigel S.
AU - Ahmad, Margaret
PY - 2012/3/12
Y1 - 2012/3/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84858020231&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84858020231&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0031867
DO - 10.1371/journal.pone.0031867
M3 - Article
C2 - 22427812
AN - SCOPUS:84858020231
VL - 7
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 3
M1 - e31867
ER -