Abstract
Gamete fusion is the climax of fertilization in all sexually reproductive organisms, from unicellular fungi to humans. Similarly to other cell-cell fusion events, gamete fusion is mediated by specialized proteins, named fusogens, that overcome the energetic barriers during this process. In recent years, HAPLESS 2/GENERATIVE CELL-SPECIFIC 1 (HAP2/GCS1) was identified as the fusogen mediating sperm-egg fusion in flowering plants and protists, being both essential and sufficient for the membrane merger in some species. The identification of HAP2/GCS1 in invertebrates, opens the possibility that a similar fusogen may be used in vertebrate fertilization. HAP2/GCS1 proteins share a similar structure with two distinct families of exoplasmic fusogens: the somatic Fusion Family (FF) proteins discovered in nematodes, and class II viral glycoproteins (e.g., rubella and dengue viruses). Altogether, these fusogens form the Fusexin superfamily. While some attributes are shared among fusexins, for example the overall structure and the possibility of assembly into trimers, some other characteristics seem to be specific, such as the presence or not of hydrophobic loops or helices at the distal tip of the protein. Intriguingly, HAP2/GCS1 or other fusexins have neither been identified in vertebrates nor in fungi, raising the question of whether these genes were lost during evolution and were replaced by other fusion machinery or a significant divergence makes their identification difficult. Here, we discuss the biology of HAP2/GCS1, its involvement in gamete fusion and the structural, mechanistic and evolutionary relationships with other fusexins.
Highlights
The merging of the plasma membranes of two independent cells with the subsequent formation of an individual cell containing both cytoplasmic contents mixed is known as cell-cell fusion
HAP2/GCS1 shares an overall three-dimensional structure with the somatic Fusion Family (FF) proteins discovered in nematodes (Mohler et al, 2002; Sapir et al, 2007; Pérez-Vargas et al, 2014) and with class II viral glycoproteins (Fédry et al, 2017; Pinello et al, 2017; Valansi et al, 2017)
Previous studies have shown FF proteins, like C. elegans’ EFF-1 (CeEFF-1), and HAP2/GCS1 are structurally homologous to viral class II fusion proteins and display a trimeric, postfusion hairpin conformation consisting of three β-sheet-rich domains (DI, DII, DIII) (Figure 1) (Pérez-Vargas et al, 2014; Fédry et al, 2017; Pinello et al, 2017; Valansi et al, 2017)
Summary
The merging of the plasma membranes of two independent cells with the subsequent formation of an individual cell containing both cytoplasmic contents mixed is known as cell-cell fusion This biological process is mediated and finely controlled by fusion proteins, termed fusogens, which are specialized proteins capable of overcoming the energetic barriers required for the fusion to occur (Chernomordik and Kozlov, 2003) and are both necessary and sufficient to mediate membrane merging (Brukman et al, 2019). The first gamete fusogen identified was HAPLESS 2/GENERATIVE CELL-SPECIFIC 1 (HAP2/GCS1) that catalyzes fertilization in flowering plants, protists and probably in some invertebrates This protein was originally found as an essential sperm factor required for male fertility in flowering plants (Johnson et al, 2004; Mori et al, 2006; von Besser et al, 2006) being later shown that it is necessary for mating in Chlamydomonas and Plasmodium (Hirai et al, 2008; Liu et al, 2008). The Arabidopsis HAP2/GCS1 (AtHAP2/GCS1) was shown to be sufficient to induce fusion of mammalian cells in culture and the infection of enveloped virus to cells (Valansi et al, 2017)
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