Sex Pheromone Production in the Silkworm,Bombyx mori, Is Mediated by Store-Operated Ca²⁺Channels

Bombyx mori Homologs of STIM1 and Orai1 Are Essential Components of the Signal Transduction Cascade That Regulates Sex Pheromone Production

“…The molecular mechanisms underlying how the extracellular signal of PBAN is transmitted into the biological response of sex pheromone production has been the focus of numerous studies. It has been well established that regardless of species, pheromonotropic activity is dependent on extracellular Ca 2ϩ (2), suggesting that PBAN signaling is associated with the influx of extracellular Ca 2ϩ ; we directly demonstrated this crucial event in Bombyx mori using fluorescent Ca 2ϩ imaging techniques (4). Early pharmacological studies in heliothine species suggested that PBAN triggers the opening of receptor-operated Ca 2ϩ channels (ROCs) (5,6).…”

“…For most female moths, sex pheromone production is dependent on an influx of extracellular Ca 2ϩ (2,4), presumably via ROCs (5,6). We have recently shown in B. mori that PBAN binding triggers the opening of SOCs (4), suggesting the possible involvement of STIM1 and Orai1; two proteins that have been identified as essential components of SOC pathways (12)(13)(14)(15).…”

“…The involvement of ROCs was strengthened when the PBAN receptor (PBANR) was identified as a G protein-coupled receptor that could function upstream of Ca 2ϩ influx when heterologously expressed in cultured insect cells (7,8). We recently expanded on the ROC studies and reported that in B. mori the PBAN pathway proceeds via store-operated channels (SOCs): sex pheromone production is blocked by classical SOC inhibitors, activators of diacyl glycerol-dependent channels are ineffective, and the pheromonotropic effects of PBAN can be mimicked by thapsigargin (TG) (4). The pheromonotropic effects of TG observed in other moth species suggest that the involvement of SOCs is likely conserved (9).…”

Molecular Mechanisms Underlying Sex Pheromone Production in Moths

“…[66][67][68] Recently we expanded on those RACC studies and reported that in B. mori the PBAN pathway proceeds via SOCs. 60) The influx of extracellular Ca 2þ through SOCs occurs in response to depletion of ER Ca 2þ stores, which is triggered by an elevation in IP 3 levels following receptor-linked PLC activation. 69,70) To examine this aspect of the signal cascade, we analyzed IP 3 levels by a conventional method that measures total inositol phosphates by blocking inositol recycling in the presence of LiCl 2 , an inhibitor of inositol monophsopahatase, and found that there was a significant increase in the levels of PG total inositol phosphates following PBAN stimulation (Hull et al, manuscript submitted).…”

“…In conjunction with the findings that sex pheromone production is blocked by classical SOC inhibitors, that activators of diacyl glycerol-dependent channels are ineffective, and that the pheromonotropic effects of PBAN can be mimicked by thapsigargin (Tg), all these data supported the hypothesis that PBAN signaling utilizes the canonical SOC activation pathway. 60) Recent discoveries have identified two proteins essential to the SOC pathway: stromal interaction molecule 1 (STIM1) and Orai1. 71,72) STIM1 is a single transmembrane (TM) domain protein that resides in the ER membrane.…”