Figure 3. Molecular players for direct gamete interactions in Arabidopsis thaliana and mammals.

(A) Arabidopsis cell surface proteins involved in gamete interaction. GAMETE EXPRESSED 2 (GEX2) on the sperm, containing extracellular immunoglobulin (Ig)-like filamin repeat domains, is required for gamete adhesion. Sperm cell-expressed GCS1/HAP2 is a single transmembrane domain (TMD) protein containing two cysteine-rich regions (C-1 and C-2) and a HAP2/GCS1-specific domain (H/G), separated by a less well-conserved region. GCS1/HAP2 is essential for gamete fusion and it´s relocation from the sperm endomembrane system to the plasma membrane is induced by EC1, a small cysteine-rich protein secreted by the egg cell upon sperm cell delivery. Putative interaction partners are depicted in light gray. (B) Mammalian cell surface proteins involved in gamete interaction. Fertilization-essential IZUMO1 of sperm contains one Izumo domain (IZ) at its N-terminus and one extracellular Ig-like domain. The binding partner of IZUMO1 on the oocyte is the GPI-anchored folate receptor 4 (Folr4) named Juno. Tetraspanin CD9 accumulates at the fusion site upon IZUMO1-Juno interaction and interacts laterally with other membrane proteins on the egg (e.g., integrins) through its larger extracellular loop. CD9/CD81 [137] double knock out mice are completely infertile, suggesting an overlapping role for these two tetraspanins during gamete fusion. Other proteins supporting sperm-egg interactions are integrin α6β1 (present on egg and sperm), the ADAM (A Disintegrin and A Metalloprotease) protein family on the sperm membrane and CRISPs (Cysteine-Rich Secretory Proteins) associating with the sperm surface when they transit the epididymis.