Conserved Mechanisms of Gamete Fusion

We established that the membrane fusion reaction in Chlamydomonas requires a species-specific protein for membrane adhesion, and a conserved protein, HAP2, for membrane merging. In collaborative studies with Drs. Robert Sinden of Imperial College, London, and Oliver Billker of Sanger Genome Center, Cambridge, UK, we showed that the malaria organism Plasmodium also uses the HAP2 gene for the membrane fusion reaction during fertilization in the gut of the mosquito (Liu et al, 2008).

Because fertilization is essential for migration of Plasmodium cells to the mosquito salivary glands, HAP2 is a target for a transmission blocking malaria vaccine. HAP2 is also present in most if not all higher plants and had been shown to required for fertilization in Arabidopsis.

Our work in Chlamydomonas and Plasmodium combined with the findings in higher plants established that the HAP2 protein is likely a conserved membrane fusogen. 

Membrane adhesion without fusion in mt+ and mt- gametes (from Liu et al, 2008)

The plus and minus gametes in the TEM images above are undergoing membrane adhesion by interaction between the species-specific membrane protein, FUS1, on the plus gamete and its unknown receptor on the minus gamete. These cells are unable to complete membrane fusion because the minus gamete is a mutant that lacks HAP2. In current studies we are identifying the receptor for FUS1 and studying the domains of HAP2 required for its function.