Neuropeptide signaling mechanisms in crustacean and insect molting glands

Abstract

Growth in arthropods requires the periodic synthesis of a new exoskeleton and shedding, or molting, of the old exoskeleton. Both processes are initiated and coordinated by ecdysteroid molting hormones synthesized and secreted by a pair of molting glands: Y-organ (YO) in decapod crustaceans and the prothoracic gland (PG) in insects. The primary regulation of arthropod molting glands is mediated by brain neuropeptides that either stimulate (prothoracicotropic hormone – PTTH – in insects) or inhibit (molt-inhibiting hormone – MIH – in crustaceans) ecdysteroidogenesis. Both neuropeptide signaling pathways involve Ca²⁺/calmodulin (CaM) and cyclic nucleotides. In the crustacean YO, the MIH signaling pathway is proposed to have two phases: a cAMP/CaM-dependent “triggering” phase that activates a NO/cGMP-dependent “summation” phase to repress ecdysteroidogenesis during most of the intermolt period. A model is presented that incorporates the following data: (1) there is a pulsatile release of MIH from the eyestalk neurosecretory center; (2) MIH has a short half-life (5–10 min) in the hemolymph; and (3) there is a decrease in sensitivity of the YO to MIH that occurs during the premolt period. Molting is initiated by a temporary reduction in MIH titers due to a decrease in the amount and/or frequency of MIH released. During premolt, an increase in MIH release that is linked to a cAMP-dependent and cGMP-independent stimulation of protein synthesis drives an increase in molting hormone synthesis. By contrast, PTTH stimulates PG ecdysteroidogenesis by a Ca²⁺-dependent activation of cAMP and mitogen-activated protein (MAP) kinase pathways. A hypothetical scheme of how these two diametrical regulatory mechanisms may have originated and evolved is presented. It assumes that both systems evolved from a common ecdysozoan ancestor that had a cAMP-dependent stimulatory pathway antagonized by a NO/cGMP-dependent inhibitory pathway. This “parallel” arrangement of the two pathways regulates ecdysteroidogenesis in the gonad of adult insects. In insect PG, cAMP-dependent signaling became the dominant pathway and NO/cGMP-dependent signaling was lost. MAP kinase signaling was later co-opted as an ancillary pathway. This dual pathway occurs in lepidopteran species (Manduca sexta and Bombyx mori), but MAP kinase signaling is the dominant pathway in Drosophila melanogaster. In crustacean YO, the cAMP- and NO/cGMP-dependent pathways became arranged in series such that a transient increase in cAMP triggers a large and sustained increase in cGMP, which leads to prolonged repression of ecdysteroidogenesis during the intermolt period. It is now recognized that the control of molting involves a constant communication between the nervous system and the molting gland mediated by a variety of endocrine factors. Both the YO and PG undergo changes in sensitivity to MIH and PTTH, respectively, that are associated with the commitment to molt. It is not surprising, however, that the changes in sensitivities of the two glands to their respective neuropeptides are opposite: the PG is the most sensitive to PTTH, whereas the YO is least sensitive to MIH, prior to and during the large peak in hemolymph ecdysteroid titers that triggers molting. As more research is conducted, we anticipate that more similarities in the neuropeptide signaling pathways of crustacean and insect molting glands will be revealed.