PP1γ1 is unable to substitute for the mammal-specific PP1γ2 isoform to support male fertility and sperm function.

The serine-threonine phosphatase has four paralogs - PP1α, PP1β, PP1γ1 and PP1γ2 - encoded by three genes, Ppp1ca, Ppp1cb, and Ppp1cc. Protein phosphatase PP1γ2, one of two isoforms of the gene Ppp1cc, is expressed in spermatogenic cells in testis and sperm, while PP1γ1 is found in somatic cells. The two PP1γ isoforms, formed by alternate splicing which occurs only in mammals, are identical except at their C-termini.

Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals.

In mammals, motility and fertilizing ability of spermatozoa develop during their passage through the epididymis. After ejaculation, sperm undergo capacitation and hyperactivation in the female reproductive tract - a motility transition that is required for sperm penetration of the egg. Both epididymal initiation of sperm motility and hyperactivation are essential for male fertility.

Cyclic AMP and glycogen synthase kinase 3 form a regulatory loop in spermatozoa.

The multifaceted glycogen synthase kinase (GSK3) has an essential role in sperm and male fertility. Since cyclic AMP (cAMP) plays an important role in sperm function, we investigated whether GSK3 and cAMP pathways may be interrelated. We used GSK3 and soluble adenylyl cyclase (sAC) knockout mice and pharmacological modulators to examine this relationship.

Isoform-specific requirement for GSK3α in sperm for male fertility.

Glycogen synthase kinase 3 (GSK3) is a highly conserved protein kinase regulating key cellular functions. Its two isoforms, GSK3α and GSK3β, are encoded by distinct genes. In most tissues the two isoforms are functionally interchangeable, except in the developing embryo where GSK3β is essential.