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Just in Time for Christmas: Gift of the MAGi - for the Virgin!

December 24, 2009 - 20:28 -- Mark Benedict

Targets for vector control have usually exploited serendipitous findings such as ion channels and hormonal control of development. However, the modern trend to search for specific targets for intervention is bearing fruit. Rogers et al. (PLOS Biology: http://tinyurl.com/yflntb6) deliver a delightful and elegant gift that arrives just in time for the holiday season and which was discovered during such a deliberate search. As part of a targeted study of proteins involved in anopheline mating, the Imperial College/Univ. Perugia team used reproductive organ proteomics (or as I like to call it, the “sexome”), genomics, RNAi and bioassays to reveal an important interaction between a major structural protein of the mating plug “Plugin” and a cross-linking protein, the male accessory gland (MAG) transglutaminase, “TGase.” The role of these in insemination of virgin females and their re-mating was investigated. Those who are interested will want to see the original manuscript for a discussion of the proteomics, genomics and phylogenetic analysis, all of which are unusually enlightening. But cutting right to the heart of their results, by knocking down An. gambiae TGase activity using RNAi injections, they demonstrated that TGase is necessary for proper plug formation and sperm storage. While I am reluctant to nitpick such a nice piece of work, less convincing to me is their claim that a plug is a not a barrier to re-insemination. Based on the description of the experimental protocol, it is clear that a plug does not prevent immediate re-insemination. However, previous studies have shown that re-insemination frequency depends on the mating protocol. Marc Klowden demonstrated that re-matings are much more common soon after the first rather than later (J. Ins. Physiol. doi:10.1016/j.jinsphys.2006.03.006). Perhaps the plug is not sufficiently firm (or the female is not yet refractory) to prevent re-mating until some hours after insertion. The likelihood of mating only once the first evening a female enters a swarm (behavior) combined with delayed hardening of the plug (biochemistry) may minimize multiple mating such as is observed naturally. This is a simple question that I suspect the team will resolve if they have not done so already. At a minimum, they have convincingly demonstrated that a newly inserted plug is not an efficient re-mating barrier. For control purposes, what might be mined from these findings? At a minimum, the team is assembling an extremely detailed body of information about the mechanics and biochemistry of anopheline mating. Interfering with TGase activity could have very strong effects of reducing population growth rate in the same way that sterile insect technique and its variants do. If a specific TGase inhibitory factor could be synthesized and delivered, a chemosterilization-like effect would be accomplished. Even if TGase inhibition promotes re-mating, an area-wide control effort in which a large majority of males have been chemosterilized could still be effective. If the expression of the TGase could be regulated in a transgenic system, such males might be useful for producing males for a transgenic version of sterile insect technique. Like the best Christmas presents, the fun is not simply opening this one, but imagining what one can do with it!