Tssk6 is required for Izumo relocalization and gamete fusion in the mouse

Abstract

One of the most important processes in fertilization is the fusion of egg and sperm; however, the molecular mechanisms involved in this process are not well understood. So far, using genetic approaches, only two proteins have been demonstrated to be necessary for this process: Izumo in sperm and CD9 in the egg. Here we demonstrate that sperm produced by Tssk6 (Sstk)-null mice present defects that prevent the successful fertilization of eggs in vitro and the fusion to zona-pellucida-free eggs. Tssk6 is a member of the testis-specific serine kinase family of proteins and is expressed postmeiotically in male germ cells. In order for fusion to occur, during the process known as acrosome reaction Izumo needs to relocate from the anterior head to other regions, including the postacrosomal compartment. Tssk6-null sperm fails to relocate Izumo during the acrosome reaction. Agents that interfere with actin dynamics blocked the acrosome-reaction-associated translocation of Izumo that is required for fusion in wild-type sperm. Additionally, actin polymerization was compromised in Tssk6-null sperm. Taken together, our results indicate that Tssk6 is involved in sperm-egg fusion through the regulation of actin polymerization and changes in Izumo localization.

Identification of a Novel HSP70-binding Cochaperone Critical to HSP90-mediated Activation of Small Serine/Threonine Kinase

“…Targeted deletion of the casein kinase 2␣Ј catalytic subunit leads to oligozoospermia and extensive degeneration of germ cells at all stages of spermatogenesis (5), and Cdk2 is essential for completing mitotic division in germ cells (6). Three members of the testis-specific serine threonine kinase (TSSK) 2 family, namely TSSK1, TSSK2, and the small serine/threonine kinase (SSTK, also known as TSSK6), are expressed postmeiotically and are essential for male fertility (7)(8)(9)(10)(11)(12)(13).…”

“…Targeted deletion of Sstk in mice resulted in male infertility without any other visible somatic defects. SSTK-null sperm could not fertilize eggs in vitro and are incapable of fusing with eggs that lack zona pellucida (9). SSTK expression first appears in elongating spermatids as they undergo cellular remodeling and chromatin condensation, and the kinase is retained in mature sperm.…”

Fertilization and the oocyte-to-embryo transition in C. elegans

“…Before coming in contact with the egg plasma membrane, IZUMO1 undergoes a relocalization event during the acrosome reaction (51,53,55). The acrosome reaction is somewhat analogous to the MO fusion in C. elegans sperm and only acrosome-reacted sperm are able to fuse with the egg.…”

“…This results in a reorganization of the plasma membrane of the sperm head and a change in localization of multiple proteins (56). IZUMO1 is localized in the acrosome prior to the acrosome reaction and relocalizes to the equatorial region after the acrosome reaction (51,53,55). The redistribution of IZUMO1 after the acrosome reaction requires a testis-specific serine kinase, TSSK6.…”

“…The redistribution of IZUMO1 after the acrosome reaction requires a testis-specific serine kinase, TSSK6. Mice deficient in TSSK6 are infertile and sperm from these mice are unable to fuse with eggs (55).…”