The previously drawn trajectory was automatically excised using the precisely focused UV-laser beam

Ltd, Cellular Microbiology, 17, 451466 Malaria infection of the mosquito protein PfHP1 and the ABC transporter-encoding gene gabcg2 increase the proportion of gametocytes in bloodstage infections. Perhaps the closest we have come to understanding these pathways is through the production and characterization of mutations resulting in the loss of gametocyte formation. The genetic regulation of gametocytogenesis was first appreciated in studies correlating the loss of chromosomal integrity with the loss of sexual potential, but it was transposon-mediated mutagenesis that identified 16 loci, nine of whose disruption led to loss of any identifiable gametocytes and seven loci essential to formation of stage II gametocytes. Of these 16 `mutagenized’ loci only five were successfully complemented. Perhaps, unsurprisingly, the former nine loci were classifiable as genes encoding regulators/ signalling moieties, and the latter seven included genes with potential roles in the formation of the extensive cytoskeletal structures defining Pf gametocyte morphology. These conclusions are consistent with parallel observations that noted up-regulation of 246 gametocyte-specific gene classes in the mature gametocytes shown to include kinase/phosphatase enzymes. Genes that have been considered of particular note include pfgdv1, pfgig, pfgly and the plasma membrane transporter NPT1. Elegant recent studies have confirmed a pivotal role for ap2-g in gametocytogenesis; transcription of ap2-g is regulated by PfHP1-H3K9me3 histone modification. Pathways regulating gametocytogenesis have been reviewed; these authors suggest ap2g may regulate pfgdv1, thence pfnek4 and nek2 genes that are 453 additionally regulated by extracellular factors via cyclic adenosine monophosphate-mediated pathways. Interestingly, the protein phosphatase PPM2 has been shown to have a positive role in the determination of sex ratio . Have we identified all the key regulator of sexual differentiation, certainly not, but we are now developing the tools for doing so. Despite long-established protocols for the culture of P. falciparum gametocytes en masse and the detailed descriptions of the complex morphological changes occurring in the skeletal, cytoplasmic and nuclear organization of the parasites and in the organization of the mitochondrion and apicoplast, we remain disturbingly ignorant of the XAV-939 molecular profile of the maturing gametocyte. Transcriptomic and proteomic studies have revealed, for example, 174 male- and 258 female-enriched proteins in mature P. falciparum gametocyte preparations. The gametocyte metabolomes are incompletely PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19822663 described; indirect observations, e.g. drug sensitivity, currently suggest the immature gametocytes are more readily killed by inhibitors of RNA and protein synthesis and schizonticides than the mature gametocytes, an observation previously linked to the substantial reduction in protein synthesis/ribosome population seen in the more mature forms. To date one of the most interesting of the unexplored aspects of gametocyte biology lies in protein translation for two reasons: first, the mature female gametocyte accumulates a reported 169731 species of translationally repressed gene transcripts, which may be localized in cytoplasmic `granules’ and Guttery et al.. CDLK, cyclin-dependent-like kinase; CDPK3,4, calcium-dependent protein kinase; GAK, cyclin g-associated kinase; MAP2, mitogen-activated protein kinase; NEK2, NEK4, NimA-related kinase; PK7, protein kinas