The conserved plant sterility gene HAP2 functions after attachment of fusogenic membranes in Chlamydomonas and Plasmodium gametes

Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Genes & Development (Impact Factor: 10.8). 05/2008; 22(8):1051-68. DOI: 10.1101/gad.1656508
Source: PubMed


The cellular and molecular mechanisms that underlie species-specific membrane fusion between male and female gametes remain largely unknown. Here, by use of gene discovery methods in the green alga Chlamydomonas, gene disruption in the rodent malaria parasite Plasmodium berghei, and distinctive features of fertilization in both organisms, we report discovery of a mechanism that accounts for a conserved protein required for gamete fusion. A screen for fusion mutants in Chlamydomonas identified a homolog of HAP2, an Arabidopsis sterility gene. Moreover, HAP2 disruption in Plasmodium blocked fertilization and thereby mosquito transmission of malaria. HAP2 localizes at the fusion site of Chlamydomonas minus gametes, yet Chlamydomonas minus and Plasmodium hap2 male gametes retain the ability, using other, species-limited proteins, to form tight prefusion membrane attachments with their respective gamete partners. Membrane dye experiments show that HAP2 is essential for membrane merger. Thus, in two distantly related eukaryotes, species-limited proteins govern access to a conserved protein essential for membrane fusion.

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    • "As a result, there is a real need to identify novel potential antigens to allow the formulation of new potent TBVs in the future and to permit the potential combination of multiple immunogens in new anti-malarial vaccine formulations [22]. Two of the five currently proven, potent transmission-blocking immunogens are present on the surface of the ookinete [23] [24], whereas the other three have conformed localization on the surface of the male gamete [18] [19] [25]. Previous proteomic experimentation has resulted in the completion of a proteome of the P. berghei male gamete, with subsequent indepth bioinformatics analysis [27]. "
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    Vaccine 11/2014; 33(3). DOI:10.1016/j.vaccine.2014.11.038 · 3.62 Impact Factor
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    • "We have also found a small number of microgametes with associated DNA and some 9 + 0 axonemes (Table 1) but it is still difficult to conceive how these immotile gametes can fertilize. One hypothesis is if gametes are by chance physically touching, membrane fusion of gametes of opposite sex mediated by fusogenic proteins like HAP2 (Liu et al., 2008) – which is present in Δsas6 (Fig. S3D) – can prevail over lack of motility. "
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    Cellular Microbiology 08/2014; 17(2). DOI:10.1111/cmi.12355 · 4.92 Impact Factor
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    • "After 24 h, cells were re-suspended in fresh ookinete medium containing an anti-P28 Cy3 conjugated 13.1 monoclonal antibody staining the surface of activated female gametocytes and ookinetes and Hoechst 33342 DNA dye before being examined with a Zeiss AxioImager M2 microscope. Ookinete conversion was calculated as the percentage of ookinetes relative to all 13.1 positive cells [28]. "
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    PLoS ONE 05/2014; 9(5):e96923. DOI:10.1371/journal.pone.0096923 · 3.23 Impact Factor
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