• PMID: 26085344
• Gene Name: CFL1
• Condition: Sperm capacitation, Acrosome reaction, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Sperm capacitation, Acrosome reaction, Male infertility

The role and importance of cofilin in human sperm capacitation and the acrosome reaction

Megnagi B, Finkelstein M, Shabtay O, Breitbart H.

The spermatozoon is capable of fertilizing an oocyte only after undergoing several biochemical changes in the female reproductive tract, referred to as capacitation. The capacitated spermatozoon interacts with the egg zona pellucida and undergoes the acrosome reaction, which enables its penetration into the egg and fertilization. Actin dynamics play a major role throughout all these processes. Actin polymerization occurs during capacitation, whereas prior to the acrosome reaction, F-actin must undergo depolymerization. In the present study, we describe the presence of the actin-severing protein, cofilin, in human sperm. We examined the function and regulation of cofilin during human sperm capacitation and compared it to gelsolin, an actin-severing protein that was previously investigated by our group. In contrast to gelsolin, we found that cofilin is mainly phosphorylated/inhibited at the beginning of capacitation, and dephosphorylation occurs towards the end of the process. In addition, unlike gelsolin, cofilin phosphorylation is not affected by changing the cellular levels of PIP2. Despite the different regulation of the two proteins, the role of cofilin appears similar to that of gelsolin, and its activation leads to actin depolymerization, inhibition of sperm motility and induction of the acrosome reaction. Moreover, like gelsolin, cofilin translocates from the tail to the head during capacitation. In summary, gelsolin and cofilin play a similar role in F-actin depolymerization prior to the acrosome reaction but their pattern of phosphorylation/inactivation during the capacitation process is different. Thus, for the sperm to achieve high levels of F-actin along the capacitation process, both proteins must be inactivated at different times and, in order to depolymerize F-actin, both must be activated prior to the acrosome reaction. FAU - Megnagi, Bar AU - Megnagi B AD - The Mina & Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel. FAU - Finkelstein, Maya AU - Finkelstein M AD - The Mina & Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel. FAU - Shabtay, Ortal AU - Shabtay O AD - The Mina & Everard Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan, 5290002, Israel.