The Insect Type 1 Tyramine Receptors: From Structure to Behavior

SIMPLE SUMMARY: This review aims to describe the type 1 tyramine receptors (TAR1s) in insects with a multidisciplinary approach and might be an important tool for a wide scientific audience, including biochemists, molecular physiologists, ethologists, and neurobiologists with a biological entomology background. In fact, in the last years, TAR1 has received much attention due to its broad general interest. The review is composed of a general introduction about the tyraminergic and octopaminergic systems and the corresponding tyramine (TA) and octopamine (OA) receptors, including the recent classification as well as their brief structural and functional information. The four chapters then describe TAR1s: (1) Molecular and structural characterization, with the purpose to provide a clear biochemical overview of the receptor that ensures a well-defined TAR1 identity; (2) pharmacology, in which a clear TAR1-mediated intracellular signaling pathway is detailed; (3) physiology and behavior, focusing on the TAR1-controlled traits in insects; (4) insecticide target, in which the knowledge on TAR1 roles in insects is associated with the growing evidence about the pest management strategies based on this receptor. The conclusions summarize TAR1 features as well as future directions on which the receptor research should move. ABSTRACT: Tyramine is a neuroactive compound that acts as neurotransmitter, neuromodulator, and neurohormone in insects. Three G protein-coupled receptors, TAR1-3, are responsible for mediating the intracellular pathway in the complex tyraminergic network. TAR1, the prominent player in this system, was initially classified as an octopamine receptor which can also be activated by tyramine, while it later appeared to be a true tyramine receptor. Even though TAR1 is currently considered as a well-defined tyramine receptor and several insect TAR1s have been characterized, a defined nomenclature is still inconsistent. In the last years, our knowledge on the structural, biochemical, and functional properties of TAR1 has substantially increased. This review summarizes the available information on TAR1 from different insect species in terms of basic structure, its regulation and signal transduction mechanisms, and its distribution and functions in the brain and the periphery. A special focus is given to the TAR1-mediated intracellular signaling pathways as well as to their physiological role in regulating behavioral traits. Therefore, this work aims to correlate, for the first time, the physiological relevance of TAR1 functions with the tyraminergic system in insects. In addition, pharmacological studies have shed light on compounds with insecticidal properties having TAR1 as a target and on the emerging trend in the development of novel strategies for pest control.