Light-regulated interactions with SPA proteins underlie cryptochrome-mediated gene expression

Abstract

Cryptochromes are a class of photosensory receptors that control important processes in animals and plants primarily by regulating gene expression. How photon absorption by cryptochromes leads to changes in gene expression has remained largely elusive. Three recent studies, including Lian and colleagues (pp. 1023-1028) and Liu and colleagues (pp. 1029-1034) in this issue of Genes & Development, demonstrate that the interaction of light-activated Arabidopsis cryptochromes with a class of regulatory components of E3 ubiquitin ligase complexes leads to environmentally controlled abundance of transcriptional regulators.

Figure 1.

A light-induced conformational change in the CCE domain of plant cryptochromes inhibits COP1-mediated degradation of transcription factors. (A) In plants, the cryptochromes (CRY1 and CRY2 in Arabidopsis) control two major developmental transitions, which are controlled by the light-regulated abundance of transcription factors. In the dark, seedlings grow from their seed reserves. Upon transfer into the light, several photoreceptors, including the cryptochromes, promote photoautotrophic growth that is accompanied by major developmental adaptations, such as development of chloroplasts, expansion of the leaves, and inhibition of stem growth. Flowering in many plant species is controlled by day length. The cryptochromes, particularly CRY2 in Arabidopsis, are major contributors of photoperiodic induction of reproductive development. (B) A model depicting how plant CRY1 regulates the activity of a multimeric E3 ubiquitin ligase composed of COP1, SPA proteins, RBX1, DDB1, and cullin 4 (the latter three are not shown on the figure). Schematic depiction of the domain structure of SPA1 and CRY1. (KRD) Kinase-related domain; (CC) coiled-coil domain; (WD) WD40 repeat domain. Parts of the proteins involved in the interaction are indicated. Cryptochromes act as dimers and are composed of two domains, the PHR and the CCE, the latter of which changes conformation upon light activation. In the dark, the CCE domain comes into direct contact with COP1 but not SPA proteins. However, COP1 and SPA interact with each other, promoting E3 ubiquitin ligase activity of the complex, leading to degradation of important transcription factors such as HY5. In the light, SPA interacts directly with the CRY1 CCE domain, preventing further interaction with COP1. This inhibits E3 ligase activity, leading to the accumulation of HY5 during de-etiolation. (C) A model depicting the mechanism of CRY2-controlled CO accumulation. Schematic depiction of the domain structure of SPA1 and CRY2. (KRD) Kinase-related domain; (CC) coiled-coil domain; (WD) WD40 repeat domain. Parts of the proteins involved in the interaction are indicated. In short day conditions, the SPA/COP multimeric E3 ligase degrades the transcription factor CO. Increased day length leads to longer CRY2 activation, and thus interaction between SPA and the PHR domain of CRY2. This leads to a tighter interaction between COP1 and CRY2 and, subsequently, inhibition of ubiquitin E3 ligase activity, resulting in stabilization of CO.