Differential role of bovine serum albumin and HCO3 − in the regulation of GSK3 alpha during mouse sperm capacitation

AbstractTo become fertile, mammalian sperm are required to undergo capacitation in the female tract orin vitro in defined media containing ions (e.g. HCO3  −, Ca2+, Na+, and Cl−), energy sources (e.g. glucose, pyruvate) and serum albumin (e.g. bovine serum albumin (BSA)). These different molecules initiate sequential and concomitant signaling pathways, leading to capacitation. Physiologically, capacitation induces changes in the sperm motility pattern (e.g. hyperactivation) and prepares sperm for the acrosomal reaction (AR), two events required for fertilization. Molecularly, HCO3  − activates the atypical adenylyl cyclase Adcy10 (aka sAC), increasing cAMP and downstream cAMP-dependent pathways. BSA, on the other hand, induces sperm cholesterol release as well as other signaling pathways. How these signaling events, occurring in different sperm compartments and with diffe rent kinetics, coordinate among themselves is not well established. Regarding the AR, recent work has proposed a role for glycogen synthase kinases (GSK3α and GSK3β). GSK3α and GSK3β are inactivated by phosphorylation of residues Ser21 and Ser9, respectively, in their N-terminal domain. Here, we present evidence that GSK3α (but not GSK3β) is present in the anterior head and that it is regulated during capacitation. Interestingly, BSA and HCO3 − regulate GSK3α in opposite directions. While BSA induces a fast GSK3α Ser21 phosphorylation, HCO3 − and cAMP-dependent pathways dephosp hory...
Source: Molecular Human Reproduction - Category: Molecular Biology Source Type: research