|LEE, JAE MIN - Riken Institute|
|MATSUMOTO, SHOGO - Riken Institute|
Submitted to: Communicative and Integrative Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 1/30/2010
Publication Date: 5/1/2010
Citation: Hull, J.J., Lee, J.M., Matsumoto, S. 2010. Functional role of STIM1 and Orai1 in silkmoth (Bombyx mori) sex pheromone production. Communicative and Integrative Biology. 3(3):240-242.
Interpretive Summary: The mating behaviors of many lepidopteran pests are stimulated by sex pheromones. It is already known that the initiation of sex pheromone production in moths is dependent on an influx of calcium through a specific class of cell surface channels, but little is known about the underlying molecular mechanisms. Two proteins referred to as STIM1 and Orai1 have recently been identified in other systems as key components of calcium influx. Using homology-based cloning methods, homologs of both proteins were identified in the silkmoth Bombyx mori. Interestingly, the B. mori channel protein (BmOrai1) lacks a number of key residues identified in mammalian Orai1 proteins that play an important role in limiting the type of ions passed through the channel. In order for Orai1 to be activated, it must interact with the C terminus of STIM1. We identified a cluster of negatively charged residues in the STIM1 C terminus that are likely responsible for this interaction. We also found that Orai1 and STIM1 are activated in response to the extracellular signal (ie. pheromone biosynthesis activating neuropeptide; PBAN) that initiates sex pheromone production. This knowledge enhances our understanding of the molecular events involved in sex pheromone production and can be used to facilitate the development of biorationally designed compounds and/or methodologies that will serve as the basis for a new generation of highly selective and ecologically friendly insect control agents.
Technical Abstract: Store-operated Ca2+ influx has recently been shown to require the activation of two proteins, stromal interaction molecule 1(STIM1) and Orai1. In mammals the putative channel ion selectivity filter is thought to comprise conserved charged residues in the first and third transmembrane domains of Orai1 in addition to three residues in the first extracellular loop. The latter residues, however, are not conserved in either of the Bombyx mori Orai1 variants or in most insects, suggesting that selectivity is a relatively recent evolutionary event. In B. mori, thapsigargin-mediated STIM1 redistribution is dependent on a cluster of highly conserved basic residues (amino acids 380-385) in the C terminus that likely interact with acidic residue in the Orai1 C terminus. BmSTIM1 redistribution in vitro also occurs downstream of pheromone biosynthesis activating neuropeptide receptor activation. Activation of in vivo RNA interference mechanisms confirmed the physiological role of BmSTIM1 and Orai1 in sex pheromone production.