Cytoplasmic Travels of the Ecdysteroid Receptor in Target Cells: Pathways for Both Genomic and Non-Genomic Actions

Signal transduction of the insect steroid hormones, ecdysteroids, is mediated by the ecdysteroid receptor, EcR. In various cells of the insect Rhodnius prolixus, EcR is present in both the nucleus and the cytoplasm, where it undergoes daily cycling in abundance and cellular location at particular developmental times of the last larval instar that are specific to different cell types. EcR favors a cytoplasmic location in the day and a nuclear location in the night. This study is the first to examine the potential mechanisms of intracellular transport of EcR and reveals close similarities with some of its mammalian counterparts. In double and triple labels using several antibodies, immunohistochemistry, and confocal laser scanning microscopy, we observed co-localization of EcR with the microtubules (MTs). Treatments with either the MT-stabilizing agent taxol or with colchicine, which depolymerizes MTs, resulted in considerable reduction in nuclear EcR with a concomitant increase in cytoplasmic EcR suggesting that MT disruption inhibits receptor accumulation in the nucleus. EcR also co-localizes with the chaperone Hsp90, the immunophilin FKBP52, and the light chain 1 of the motor protein dynein. All these factors also co-localize with MTs. We propose that in Rhodnius, EcR exerts its genomic effects by forming a complex with Hsp90 and FKBP52, which uses dynein on MTs as a mechanism for daily nucleocytoplasmic shuttling. The complex is transported intact to the nucleus and dissociates within it. We propose that EcR utilizes the cytoskeletal tracks for movement in a manner closely similar to that used by the glucocorticoid receptor. We also observed co-localization of EcR with mitochondria which suggests that EcR, like its mammalian counterparts, may be involved in the coordination of non-genomic responses of ecdysteroids in mitochondria

The Coming of Age of Insulin-Signalling in Insects

The new millennium has seen a major paradigm shift in insect endocrinology. Great advancements are being made which establish that nutrition and growth play a central role in diverse cellular and physiological phenomena during insect development and reproduction. Nutrition affects rates of growth and is mainly regulated by the function of the pathway of insulin/insulin-like growth factor signalling. This pathway is highly conserved across species and ultimately regulates rates of cell growth and proliferation in growing organs. Insulin and insulin-like peptides (ILPs) are some of the best studied hormones in the animal kingdom and all share a common structural motif and initiate a wide range of closely similar physiological processes in higher organisms. In insects, nutrition, via circulating sugar, promotes release of ILPs from brain neurosecretory cells into the haemolymph, which act on peripheral tissues and stimulate protein synthesis and cell growth. Therefore, insect ILPs are common mediators between nutrition and growth in insects and are functionally analogous to mammalian insulin. The 1980s and 1990s witnessed great progress in elucidation of the physiological and molecular mechanism of action of numerous insect hormones involved in regulation of growth, development, reproduction and metabolism. But the signals for the initiation or termination of controlled events remained largely unknown. ILPs were first identified from the silkmoth Bombyx mori and were named bombyxins, but related peptides were soon found in numerous species and their functions elucidated. The insulin signalling pathway is now recognized as a central factor in the timing of cell proliferation, growth, longevity, reproduction, and reproductive diapause, as well as social behaviour. Recent work has revealed that the insulin signalling pathway is closely integrated with that of various other hormones, including ecdysteroids, the juvenile hormones and neuropeptide(s) such a prothoracicotropic hormone. In addition, the pathway is also linked with both circadian (daily) and photoperiodic (seasonal) clocks potentially providing a basis for its timing function. This Research Topic aims to provide the only current collection of recent advances on insect ILPs. We encouraged submissions on all areas related to identification, characterization, regulation and physiological functions of insect ILPs. We welcomed both full and short reviews and original research articles

Non-genomic ecdysone effects and the invertebrate nuclear steroid hormone receptor EcR--new role for an "old" receptor?

International audienceThe ecdysteroids (Ec), invertebrate steroid hormones, elicit genomic but also non-genomic effects. By analogy to vertebrates, non-genomic responses towards Ec may be mediated not only by distinct membrane-integrated but also by membrane-associated receptors like the classical nuclear ecdysteroid receptor (EcR) of arthropods. This is supported by a comparison of physiological properties between invertebrate and vertebrate steroid hormone systems and recent findings on the subcellular localization of EcR. The measured or predicted high degree of conformational flexibility of both Ec and the ligand binding domain (LBD) of EcR give rise to a conformational compatibility model: the compatibility between conformations of the cognate receptor's ligand binding domain and structures or conformations of the ligand would determine their interaction and eventually the initiation of genomic versus non-genomic pathways. This model could also explain why specific non-genomic effects are generally not observed with non-steroidal agonists of the bisacylhydrazine group