• PMID: 20711218
• Gene Name: EZR
• Condition: Assocaited with sperm capacitation
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Assocaited with sperm capacitation

The role of ezrin-associated protein network in human sperm capacitation

Wang L, Chen W, Zhao C, Huo R, Guo XJ, Lin M, Huang XY, Mao YD, Zhou ZM, Sha JH.

Membrane modifications in sperm cells represent a key step in sperm capacitation; however, the molecular basis of these modifications is not fully understood. Ezrin is the best-studied member of the ezrin/radixin/merlin family. As a cross-linker between the cortical cytoskeleton and plasma membrane proteins, ezrin contributes to remodeling of the membrane surface structure. Furthermore, activated ezrin and the Rho dissociation inhibitor, RhoGDI, promote the formation of cortical cytoskeleton-polymerized actin through Rho activation. Thus, ezrin, actin, RhoGDI, Rho and plasma membrane proteins form a complicated network in vivo, which contributes to the assembly of the structure of the membrane surface. Previously, we showed that ezrin and RhoGDI1 are expressed in human testes. Thus, we sought to determine whether the ezrin-RhoGDI1-actin-membrane protein network has a role in human sperm capacitation. Our results by Western blot indicate that ezrin is activated by phosphorylation of the threonine567 residue during capacitation. Co-immunoprecipitation studies revealed that, during sperm capacitation, the interaction between ezrin and RhoGDI1 increases, and phosphostaining of two dimensional electrophoresis gels showed that RhoGDI1 is phosphorylated, suggesting that RhoGDI1 dissociates from RhoA and leads to actin polymerization on the sperm head. We speculate that activated ezrin interacts with polymerized actin and the glycosylated membrane protein cd44 after capacitation. Blocking sperm capacitation using ezrin- or actin-specific monoclonal antibodies decreases their acrosome reaction (AR) rate, but has no effect on the AR alone. Taken together, our results show that a network consisting of ezrin, RhoGDI1, RhoA, F-actin and membrane proteins functions to influence the modifications that occur on the membrane of the sperm head during human sperm capacitation. FAU - Wang, Lei AU - Wang L AD - Laboratory of Reproductive Medicine, Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China. FAU - Chen, Wen AU - Chen W FAU - Zhao, Chun AU - Zhao C FAU - Huo, Ran AU - Huo R FAU - Guo, Xue-Jiang AU - Guo XJ FAU - Lin, Min AU - Lin M FAU - Huang, Xiao-Yan AU - Huang XY FAU - Mao, Yun-Dong AU - Mao YD FAU - Zhou, Zuo-Min AU - Zhou ZM