Document Detail

Human cryptochrome-1 confers light independent biological activity in transgenic Drosophila correlated with flavin radical stability.
MedLine Citation:
PMID:  22427812     Owner:  NLM     Status:  MEDLINE    
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.
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
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-03-12
Journal Detail:
Title:  PloS one     Volume:  7     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2012  
Date Detail:
Created Date:  2012-03-19     Completed Date:  2012-08-20     Revised Date:  2013-06-26    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e31867     Citation Subset:  IM    
Université Paris VI, Paris, France.
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MeSH Terms
Animals, Genetically Modified
Circadian Rhythm / physiology*
Cryptochromes / isolation & purification,  metabolism*
DNA Primers / genetics
Flavins / metabolism*
Gene Expression Profiling
Metamorphosis, Biological / physiology*
Microarray Analysis
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / physiology*
Reg. No./Substance:
0/CRY1 protein, human; 0/Cryptochromes; 0/DNA Primers; 0/Flavins

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