IZUMO1

Izumo1 is a vertebrate sperm membrane glycoprotein essential for the fusion of sperm and oocyte during fertilization. The protein is named after the Izumo shrine in Japan, reflecting its required role in mammalian fertilization and the tradition of naming fertilization factors after Shinto symbols.

Structure and localization: Izumo1 is a type I transmembrane glycoprotein with an extracellular region that contains an immunoglobulin-like fold, a single transmembrane helix, and a short cytoplasmic tail. It is N-glycosylated and expressed on the surface of the sperm head. In mature sperm, Izumo1 localizes to the periacrosomal region and relocates to the equatorial segment following the acrosome reaction, positioning it at the site of sperm-egg contact.

Function and mechanism: Izumo1 mediates the initial binding between sperm and egg by engaging its receptor on the oocyte surface, JUNO (also known as IZUMO1R). The Izumo1–JUNO interaction is required for sperm–egg fusion, a final step in fertilization beyond acrosome reaction and sperm adhesion. In loss-of-function models, sperm can undergo acrosome reaction and adhere to the oocyte but fail to fuse, demonstrating the indispensable role of Izumo1 in fertilization.

Expression and evolution: Izumo1 is expressed in male germ cells and is conserved across many mammalian species, indicating a long-standing role in fertilization. While the primary function is fertilization, the Izumo1–JUNO axis has attracted interest as a potential target for contraceptive strategies and as a biomarker in studies of male fertility.

Clinical and research relevance: Given its essential role in fusion, Izumo1 and its interaction with JUNO are central to investigations of infertility and the development of non-hormonal contraceptives. Continued research aims to clarify additional components of the fusion machinery and regulatory mechanisms governing Izumo1 localization and activity.