Actin polymerization is a crucial process during capacitation. We have recently described the participation of FAK in actin polymerization in guinea pig spermatozoa. However, the mechanism by which FAK achieves these processes is unknown. Our data showed that ERK2 is activated during the first minutes of capacitation; its inhibition blocked actin polymerization and the acrosome reaction. Additionally, the present study found that FAK is involved in ERK2 activation since FAK was phosphorylated in Tyr925 and bound to Grb2 and that the inhibition of FAK results in a significant decrease in ERK2 activation. We also confirmed the presence of GEF-H1, which was able to associate with RhoA during capacitation. RhoA activation and its participation in actin polymerization were also analyzed. FAK or ERK1/2 inhibition impeded GEF-H1 phosphorylation, RhoA activation, and the association between GEF-H1 and RhoA. Finally, we observed the presence of fibronectin on the sperm surface, its role in sperm-sperm interaction, and the participation of β-integrin in the activation of ERK2. Our results show that the signaling pathway Fibronectin/Integrin/FAK/Grb2/MEK1/2/ERK2/GEF-H1/RhoA regulates the actin polymerization associated with spermatozoa capacitation.
Actin cytoskeleton remodeling is a critical process for the acquisition of fertilizing capacity by spermatozoa during capacitation. However, the molecular mechanism that regulates this process has not been fully elucidated. In somatic cells, Ras‐related C3 botulinum toxin substrate 1 protein (Rac1) promotes the polymerization of actin by participating in the modeling of two structures: lamellipodia and adhesion complexes linked with the plasma membrane. Rac1 is expressed in mammalian spermatozoa; however, the role of Rac1 in sperm physiology is unknown. This study aimed to elucidate the participation of Rac1 in capacitation and acrosome reaction (AR). Rac1 was found to be dispersed throughout the acrosome and without changes in the middle piece. After 60 minutes of capacitation, Rac1 was found in the apical region of the acrosome only, which concurred with an increase in Rac1‐GTP. Rac1 inhibition prevented such changes. In the middle piece, Rac1 localization remained unchanged. Besides, Rac1 inhibition blocked capacitation and AR. The present study demonstrates that Rac1 participates only in the actin cytoskeleton remodeling that occurs in the acrosomal apical region during capacitation, a region where a large amount of actin is polymerized and shaped in a diadem‐like structure. Our data also show that this actin cytoskeleton organized by Rac1 interacts with filamin‐1, and such interaction was blocked by the inhibition of Rac1, which led to a different organization of the actin cytoskeleton. All these outcomes imply that the formation of an F‐actin cytoskeleton in the acrosomal apical region is a necessary event for capacitation and AR, and which is Rac1 driven.
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