Tale of cAMP as a second messenger in auxin signaling and beyond

Abstract

The 3',5'-cyclic adenosine monophosphate (cAMP) is a versatile second messenger in many mammalian signaling pathways. However, its role in plants remains not well-recognized. Recent discovery of adenylate cyclase (AC) activity for transport inhibitor response 1/auxin-signaling F-box proteins (TIR1/AFB) auxin receptors and the demonstration of its importance for canonical auxin signaling put plant cAMP research back into spotlight. This insight briefly summarizes the well-established cAMP signaling pathways in mammalian cells and describes the turbulent and controversial history of plant cAMP research highlighting the major progress and the unresolved points. We also briefly review the current paradigm of auxin signaling to provide a background for the discussion on the AC activity of TIR1/AFB auxin receptors and its potential role in transcriptional auxin signaling as well as impact of these discoveries on plant cAMP research in general.

Keywords: adenylate cyclase; auxin signaling; cyclic adenosine monophosphate (cAMP); second messenger; transport inhibitor response 1/auxin-signaling F-box proteins (TIR1/AFBs).

Fig. 1

Chemical structure and homeostasis of cyclic nucleotide monophosphates (cNMPs). (a) Structure and homeostasis of 3′,5′‐cyclic adenosine monophosphate (cAMP). 3′,5′‐cAMP is produced from adenosine triphosphate (ATP) by adenylate cyclase (AC) and can be further hydrolyzed to adenosine 5'‐monophosphate (5′‐AMP) by cNMP phosphodiesterases (PDE). 3′,5′‐cGMP is produced from guanosine triphosphate (GTP) by guanylate cyclase (GC) and is hydrolyzed by PDE in a similar way. (b) Biogenesis of 2′,3′‐cAMP. 2′,3′‐cAMP and 2′,3′‐cGMP are produced during the hydrolysis of dsRNA/DNA.

Fig. 2

Cyclic adenosine monophosphate (cAMP) signaling in mammalian cells. Signal molecule like hormone or neurotransmitter binds to G protein‐coupled receptor (GPCR), and the associated heterotrimeric G protein is activated. The released Gα subunit binds and activates transmembrane adenylate cyclase (tmACs) to produce cAMP. Soluble AC (sAC) in cytoplasm can be activated by bicarbonate anions (HCO₃ ⁻) to produce cAMP. cAMP mediates various downstream responses through directly binding its downstream effectors and regulating their function. The well‐characterized cAMP downstream effectors include protein kinase A (PKA), cyclic nucleotide‐gated channels (CNGC), exchange protein activated by cAMP (EPAC) and Popeye domain containing proteins (POPDC). cAMP can be further hydrolyzed by PDE. Efficient cAMP hydrolysis by phosphodiesterases (PDEs) in vicinity restricts the cAMP diffusion within cells leading to formation of spatially restricted subcellular local cAMP pool. This is possibly the key ingredient assuring specificity of signal transduction. ATP, adenosine triphosphate.

Fig. 3

Cyclic adenosine monophosphate (cAMP) as the second messenger in auxin signaling. Without auxin, the adenylate cyclase (AC) activity of transport inhibitor response 1/auxin‐signaling F‐box proteins (TIR1/AFB) auxin receptors is low. The transcriptional repressors auxin/indole‐3‐acetic acid (Aux/IAAs) are stable, interact with and repress auxin response factor (ARF) transcriptional activators. Thus, auxin‐induced transcription is turned off. Auxin binding to TIR1/AFBs promotes their interaction with Aux/IAAs, leading to Aux/IAA's ubiquitination and degradation, thus releasing ARFs from their repression. Simultaneously, AC activity of TIR1/AFBs is enhanced to produce more cAMP after auxin perception, which is also crucial for the final transcriptional response. Hence, Aux/IAAs' degradation and cAMP production are two signaling outputs of the auxin perception, both required for the auxin‐induced transcription. ATP, adenosine triphosphate.