Human sperm biomarkers

Reproductive Medecine - Male Fertility

More details on the AKAP4 protein

AKAP4 is playing a central role in flagellar structure, chemotaxis, capacitation and sperm motility (Luconi et al., 2011). In mammals, AKAP4 is expressed during spermatogenesis. This 854 amino-acid protein is processed from a pro-AKAP4 (854 aa) to a “mature” AKAP4 protein lacking the 188 first amino acids (Turner et al., 1998). AKAP4 is specifically localized to the fibrous sheath of the principal piece of the flagellum a structure involved in flagellum structure and sperm motility.

AKAP4 (also named AKAP82) is a one of the major components (~50%) of the sperm fibrous sheath. The AKAP4 precursor termed proAKAP4 is processed to mature AKAP4 during sperm differentiation in the human testes (Nipper et al., 2006). The human AKAP4 gene is located on chromosome X. This gene encodes a 854 amino acid polypeptide localized in the fibrous sheath of the sperm flagellum (see application).

In the litterature, AKAP4 was previously named AKAP82, PRKA4 (Protein Kinase A Anchoring Protein 4), CT99 (Cancer/Testis Antigen 99), HI, p82, or FSC1 (Fibrous Sheath Component 1). AKAP4 (A-Kinase Anchor Protein 4) protein belongs to the family of A-kinase anchor proteins (AKAPs) all sharing a common function of binding to the regulatory subunit of protein kinase A (PKA) and confining the PKA holoenzyme to discrete locations within the cell. Therefore, AKAP4 is an essential regulator of PKA and PKC protein kinases signalling to the motor protein dynein of the axoneme of flagellum. 

AKAP4 can be serine- and tyrosine-phosphorylated in a capacitation-dependent manner in human spermatozoa but the nature of the kinases involved are not yet elucidated. Spermatozoa from mice lacking AKAP4 failed to show progressive motility and homozygous male mice are unfertile (Miki et al., 2002). Spermatozoa of male mice knocked-out of the AKAP4 gene have an abnormal fibrous sheath structure and are immotile.

The mouse monoclonal antibody anti-AKAP4 clone 7E10 (Ref. 4BDX-1602) recognizes the carboxy-terminal region of A-kinase anchor protein 4 (AKAP4) and is suitable for Western Blot, for Immunohistochemistry, ELISA, Electron Microscopy and Immunofluorescence.

Western blotting and immunocytochemistry techniques using the anti-pro AKAP4 clone 6F12 (Ref. 4BDX-1701) showed that the pro-AKAP4 is specifically expressed in human, equine, porcine, bovine murine and ovine spermatozoa.