HAL : hal-00683663, version 1

PubMed : 22427812

PubMed Central : 3299647

DOI : 10.1371/journal.pone.0031867

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PLoS ONE 7, 3 (2012) e31867

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

Jacqueline Vieira 1, Alex R Jones 2, Antoine Danon 1, Michiyo Sakuma 2, Nathalie HOANG 1, David Robles 1, Shirley Tait 2, Derren J Heyes 2, Marie Picot 3, 4, Taishi Yoshii 5, Charlotte Helfrich-Förster 6, Guillaume Soubigou 7, Jean-Yves Coppee 7, André Klarsfeld 3, 4, Francois Rouyer 3, 4, Nigel S Scrutton 2, Margaret Ahmad (  Auteur correspondant ) 1, 8

(2012)

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.

1 :	Université Pierre et Marie Curie - Paris 6 (UPMC)
	Université Pierre et Marie Curie [UPMC] - Paris VI
2 :	Manchester Interdisciplinary Biocentre and Faculty of Life Sciences
	University of Manchester
3 :	Neurobiologie et Développement (N&eD)
	CNRS : UPR3294 – Université Paris XI - Paris Sud
4 :	Institut de Neurobiologie Alfred Fessard (INAF)
	CNRS : FRC2118
5 :	Graduate School of Natural Science and Technology
	Okayama University
6 :	Biocentre, Neurobiology and Genetics
	University of Würzburg
7 :	Transcriptome et Epigénome (PF2)
	Institut Pasteur de Paris
8 :	Penn State University, Media, Pennsylvania
	Penn State University

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Contributeur : Alain Perignon <>

Soumis le : Mardi 3 Avril 2012, 11:52:33

Dernière modification le : Mardi 3 Avril 2012, 13:25:22