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Ferracchiato, S.

Publications and source records attributed to Ferracchiato, S..

2 recordsLinked to original sources

JNK signaling regulates reproductive trade-offs after Plasmodium infection in the malaria mosquito

Environmental stress can limit mammalian reproduction by affecting production of sexual steroid hormones. Here we reveal a similar mechanism in the malarial mosquito Anopheles gambiae: activation of the stress-sensitive c-Jun N-terminal kinase, JNK, constrains reproductive investment by suppressing production of ecdysteroids that orchestrate egg development in this species. We show that infection with Plasmodium berghei parasites increases JNK signalling in the reproductive tract causing a JNK-dependent reduction in both egg development and mosquito survival. Moreover, JNK signaling supresses expression of Cyp315a1 (AGAP000284), a rate-limiting enzyme in ecdysteroid synthesis, a transcriptional change reflected in reduced ecdysteroid production following an infected blood meal. A similar mechanism limits egg production under other stressors (heat stress, or ectopic activation of JNK signaling). Together, these data reveal a regulatory circuit whereby Plasmodium infection curtails reproductive investment in an important vector of human malaria, one that may be applicable to environmental stressors more generally.

zoology↗

20E-dependent tyrosine phosphorylation of phospholipase C gamma underpins egg development in the malaria vector Anopheles gambiae

The efficient development of eggs following a blood meal is central to the vector capacity of Anopheles gambiae females. The ecdysteroid hormone 20-hydroxyecdysone (20E) plays a pivotal role in this process, yet the signaling mechanisms by which 20E exerts its effects remain incompletely understood. Here we show blood feeding is associated with increased tyrosine phosphorylation of an array of proteins coincident with the increase in titers of 20E that follows a blood meal. Injection of genistein, a tyrosine kinase inhibitor, reduces both the appearance of phosphotyrosine-containing proteins and fecundity, linking tyrosine phosphorylation to egg development. We identify one of the proteins phosphorylated after a blood meal as phospholipase C gamma (PLC{gamma}) and show that its blood feeding-induced phosphorylation is dependent on endogenously synthesized 20E via the ecdysone receptor (EcR). Interruption of Src-like tyrosine kinase signaling inhibits phosphorylation of PLC{gamma} as well as egg development after blood feeding, implicating Src-like kinases in the phosphorylation of PLC{gamma}. Taken together, these data suggest that the effects of 20E on An. gambiae egg development are at least partially mediated through a tyrosine phosphorylation-dependent signaling cascade involving Src family tyrosine kinases and PLC{gamma}.

biochemistry↗