Overexpression and altered nucleocytoplasmic distribution ofAnophelesovalbumin-like SRPN10 serpins inPlasmodium-infected midgut cells.

The design of effective, vector-based malaria transmission blocking strategies relies on a thorough understanding of the molecular and cellular interactions that occur during the parasite sporogonic cycle in the mosquito. DuringPlasmodium bergheiinvasion, transcription from the SRPN10 locus, encoding four serine protease inhibitors of the ovalbumin family, is strongly induced in the mosquito midgut. Herein we demonstrate that intense induction as well as redistribution of SRPN10 occurs specifically in the parasite-invaded midgut epithelial cells. Quantitative analysis establishes that in response to epithelial invasion, SRPN10 translocates from the nucleus to the cytoplasm and this is followed by strong SRPN10 overexpression. The invaded cells exhibit signs of apoptosis, suggesting a link between this type of intracellular serpin and epithelial damage. The SRPN10 gene products constitute a novel, robust and cell-autonomous marker of midgut invasion by ookinetes. The SRPN10 dynamics at the subcellular level confirm and further elaborate the‘time bomb’ model ofP. bergheiinvasion in bothAnopheles stephensiandAnopheles gambiae. In contrast, this syndrome of responses is not elicited by mutantP. bergheiookinetes lacking the major ookinete surface proteins, P28 and P25. Molecular markers with defined expression patterns, in combination with mutant parasite strains, will facilitate dissection of the molecular mechanisms underlying vector competence and development of effective transmission blocking strategies. [ABSTRACT FROM AUTHOR]