Design principles for decoding calcium signals to generate specific gene expression via transcription

Abstract

The second messenger calcium plays a key role in conveying specificity of signalling pathways in plant cells. Specific calcium signatures are decoded to generate correct gene expression responses and amplification of calcium signatures is vital to this process. It is not known: (1) if this amplification is an intrinsic property of all calcium-regulated gene expression responses and whether all calcium signatures have the potential to be amplified, and (2) how does a given calcium signature maintain specificity in cells containing a great number of transcription factors (TFs) and other proteins with the potential to be calcium-regulated? The work presented here uncovers the design principle by which it is possible to decode calcium signals into specific changes in gene transcription in plant cells. Regarding the first question, we found that the binding mechanism between protein components possesses an intrinsic property that will nonlinearly amplify any calcium signal. This nonlinear amplification allows plant cells to effectively distinguish the kinetics of different calcium signatures to produce specific and appropriate changes in gene expression. Regarding the second question, we found that the large number of calmodulin (CaM)-binding transcription factors (TFs) or proteins in plant cells form a buffering system such that the concentration of an active CaM-binding TF is insensitive to the concentration of any other CaM-binding protein, thus maintaining specificity. The design principle revealed by this work can be used to explain how any CaM-binding TF decodes calcium signals to generate specific gene expression responses in plant cells via transcription.