The diversity of ion channel-assembled molecular switches empowers the flexibility and specificity of Ca2+ language

Abstract

Ca transport mediated by ion channels across the membrane triggers specific cytosolic calcium signals, which play pivotal roles in plant development control and multiple stress responses. CNGCs (cyclic nucleotide-gated channels, CNGCs) are a type of nonselective cation channels, which form homotetrameric or heterotetrameric complexes in the plasma membrane to generate stimulus-specific Ca signatures in plants. Recently, some exciting work from the functional characteristics of CNGC channels have revealed that multiplex combinations of different CNGC channel subunits, or dynamic interaction between channel and transporter modulate CNGC channel activity, lead to diverse regulations on the Ca signaling to participate in dedicated physiological and pathological responses in Arabidopsis thaliana. These new findings shed light on new regulatory mechanisms of CNGC channel-assembled molecular switches and expand our knowledge of how plants efficiently adapt to ever-changing endogenous and external environments. Calcium ions (Ca), serving as a second messenger, play the fundamental function in living cells. Existing evidence shows that under the stimulation of various endogenous and exogenous cues, ion channels distributed on plasma membrane and endomembrane system of the cell are activated transiently, which mediates Ca transport from the extracellular or intracellular calcium pools and gives rise to a rapid elevation in cytosolic free Ca concentration ([Ca]cyt). The fluctuations of [Ca]cyt formulate universal but specific calcium signals, also known as Ca signatures, to engage in a wide range of essential cellular physiological and pathological processes, such as initiation of early developmental events, rhythmic regulation, hormone signaling, biotic and abiotic stress responses. However, since the long-term high Ca concentration in the cytosol shows serious cytotoxic effects, the [Ca]cyt must be maintained at sufficiently low levels around 100 nM under normal physiological conditions. Hence, to ensure the security, efficiency and precise nature of Ca signaling, the spatial and temporal dynamic changes of [Ca]cyt are stringently supervised by a refined regulatory network that includes an array of energy-coupled transporters, channels, cellular Ca sensors and some unidentified molecular players that have not been well established yet. In the past several decades, the extensive and collaborative efforts aimed at identifying Ca signaling machinery, coupled with a diverse array of signals and responses, have been made in plant science research. A large number of Ca-permeable channels with determined specificity of Ca signals showing in the frequency, amplitude and spatial distribution of the [Ca ]cyt oscillations have been isolated and characterized, which significantly enriches our understanding in the structural and functional properties of plant ion channels. Nevertheless, the highly dynamic involvement and electrophysiological properties of molecular switches assembled by ion channels and membrane compartments, termed Ca signature encoders, have not been well documented. Our recent work demonstrates that several such molecular switches composed of different subunits of cyclic nucleotide-gated channels (CNGCs), with great physiological significance, specifically modulate the spatial and temporal propagation of Ca signals. The calcium oscillator composed of CNGC8/7, CNGC18 and CaM2/3 manifests calcium-dependent on–off cycling in maintaining the highly complex spatio-temporal patterns of [Ca]cyt oscillations at the tip of the pollen tube, which provides an autoregulatory feedback mechanism for calcium oscillations during the polarized rhythmic growth of pollen tube (Figure 1a). Additionally, we have identified that the functional channel combination of CNGC2 and CNGC4 gated by calmodulins (CaMs) is involved in the PAMP-triggered immunity signaling pathway in Arabidopsis thaliana, which builds a critical link between the pattern-recognition receptor complex and calcium-dependent immunity programs (Figure 1b). These calcium signal encoders function through a new and effective strategy, with a variety of CNGCs interactions facilitated by CaMs/RLKs regulation, to perceive and switch the diversity of endogenous and external cues into the unique cytosolic Ca language. More recently, we discovered that CNGC15 and the nitrate transporter NRT1.1 (CHL1/NPF6.3) constitute a new type of molecular switch controlling calcium influx with a nitrate-