Characterization of mouse sperm TMEM190, a small transmembrane protein with the trefoil domain: evidence for co-localization with IZUMO1 and complex formation with other sperm proteins.

TMEM190, a small transmembrane protein containing the trefoil domain, was previously identified by our proteomic analysis of mouse sperm. Two structural features of TMEM190, 'trefoil domain' and 'small transmembrane protein', led us to hypothesize that this protein forms a protein-protein complex required during fertilization, and we characterized TMEM190 by biochemical, cytological, and genetic approaches. We showed in this study that the mouse Tmem190 gene exhibits testis-specific mRNA expression and that the encoded RNA is translated into a 19-kDa protein found in both testicular germ cells and cauda epididymal sperm.

Testase 1 (ADAM 24) a sperm surface metalloprotease is required for normal fertility in mice.

ADAM family members play important roles in various physiological and pathological processes, for example, fertilization, embryogenesis, neurogenesis, and development of asthma and arthritis (Primakoff and Myles, 2000. Trends Genet 16: 83-87; Edwards et al., 2008.

Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm.

Izumo, a sperm membrane protein, is essential for gamete fusion in the mouse. It has an Immunoglobulin (Ig) domain and an N-terminal domain for which neither the functions nor homologous sequences are known. In the present work we identified three novel proteins showing an N-terminal domain with significant homology to the N-terminal domain of Izumo.

Loss of surface EWI-2 on CD9 null oocytes.

CD9, a member of the tetraspanin family, associates with a variety of other proteins to form the tetraspanin web. CD9 forms direct and relatively stable associations with the immunoglobulin superfamily proteins EWI-2 and EWI-F. Deletion of the Cd9 gene results in female infertility since Cd9 null mice produce oocytes that fail to fuse.