Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm
Article first published online: 5 AUG 2009
Copyright © 2009 Wiley-Liss, Inc.
Molecular Reproduction and Development
Volume 76, Issue 12, pages 1188–1199, December 2009
How to Cite
Ellerman, D. A., Pei, J., Gupta, S., Snell, W. J., Myles, D. and Primakoff, P. (2009), Izumo is part of a multiprotein family whose members form large complexes on mammalian sperm. Mol. Reprod. Dev., 76: 1188–1199. doi: 10.1002/mrd.21092
- Issue published online: 15 OCT 2009
- Article first published online: 5 AUG 2009
- Manuscript Accepted: 8 JUL 2009
- Manuscript Received: 25 MAR 2009
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. We named this region “Izumo domain,” and the novel proteins “Izumo 2,” “Izumo 3,” and “Izumo 4,” retaining “Izumo 1” for the first described member of the family. Izumo 1–3 are transmembrane proteins expressed specifically in the testis, and Izumo 4 is a soluble protein expressed in the testis and in other tissues. Electrophoresis under mildly denaturing conditions, followed by Western blot analysis, showed that Izumo 1, 3, and 4 formed protein complexes on sperm, Izumo 1 forming several larger complexes and Izumo 3 and 4 forming a single larger complex. Studies using different recombinant Izumo constructs suggested the Izumo domain possesses the ability to form dimers, whereas the transmembrane domain or the cytoplasmic domain or both of Izumo 1 are required for the formation of multimers of higher order. Co-immunoprecipitation studies showed the presence of other sperm proteins associated with Izumo 1, suggesting Izumo 1 forms a multiprotein membrane complex. Our results raise the possibility that Izumo 1 might be involved in organizing or stabilizing a multiprotein complex essential for the function of the membrane fusion machinery. Mol. Reprod. Dev. 76: 1188–1199, 2009. © 2009 Wiley-Liss, Inc.