Of ATP receptors, opioid receptors, and AKAP regulation of calcium channels

This month's installment of Generally Physiological concerns the identification of a previously unknown type of purinergic receptor in plants, differential regulation of calcium channels by two different AKAP proteins, and sodium regulation of opioid receptors. Initially greeted with skepticism, the notion that ATP plays a role in mam-malian extracellular signaling is now generally accepted, an acceptance facilitated by identification of plasma membrane P2-type purinergic receptors , which recognize and respond to extracellular ATP. Various lines of evidence suggest that ATP also acts as an extracellular signal in plants; however, attempts to identify plant ATP receptors similar to either P2X receptors (a family of ligand-gated channels) or P2Y receptors (a family of GPCRs) have been unsuccessful. Choi et al. (2014) screened 50,000 mutagenized Arabidopsis seedlings and identified two allelic mutants, which they named Does not Respond to Nucleotides 1-1 (dorn1-1) and dorn1-2, which failed to show the increase in intracellular calcium elicited by ATP in wild-type plants. Unlike wild-type plants, dorn1-1 mutants failed to phosphorylate mito-gen-activated protein kinase (MPK)3 and MPK6 in response to ATP, and mi-croarray analysis identified more than 500 genes that responded to ATP in wild-type plants but not in the dorn1-1 mutant. The dorn1 mutations occurred in the kinase domain of a gene that encoded a protein with an ex-tracellular lectin domain, a single transmembrane domain, and an in-tracellular kinase domain known to be localized to the plasma membrane. Ectopic expression of the wild-type protein restored the calcium response to ATP to dorn1-2 mutants; moreover, recombinant DORN1 protein bound ATP with a dissociation constant of 45.7 ± 3.1 nM. The authors thus propose that DORN1 is essential for Arabidopsis perception of extracellu-lar ATP, and may be the founding member of a family of plant-specific purinergic receptors. Calcium entry through the voltage-gated calcium channels Cav1.1 and Cav1.2 initiates various cellular processes, including excitation–con-traction coupling in muscle and excitation–transcription coupling in neurons. -adrenergic signaling leads to activation of protein kinase A (PKA), which phosphorylates Cav1.1 and Cav1.2, thereby increasing their activity (and consequently muscle contractile force) during the sympathetic fight-or-flight response. A kinase anchoring protein 15 (AKAP15), which binds to the distal C-terminal domain of Cav1.1 and Cav1.2, enables their phosphoryla-tion by recruiting PKA. In this issue, noting that AKAP79, which binds the protein phosphatase calcineu-rin, binds to the same site as AKAP15 on the distal C-terminal domain (DCT), Fuller et al. used a reconstituted system to explore the …