Molecular genetic analysis of two human sperm fibrous sheath proteins, AKAP4 and AKAP3, in men with dysplasia of the fibrous sheath

Dysplasia of the fibrous sheath (DFS) is characterized by male infertility, asthenozoospermia, and morphologically abnormal flagella that possess a se verely malformed fibrous sheath. in many cases, DFS is familial, suggesting a genetic component. Human AKAP4 and AKAP3 are structural proteins of the fibrous sheath that also function to anchor protein kinase A to this struct ure via the regulatory subunit of the kinase. We hypothesized that defects in either AKAP4 or AKAP3 might cause DFS. No quantitative or qualitative di fferences between patients with DFS and normal controls were detected when sperm proteins were analyzed by either silver staining or immunoblot analys is using antibodies raised against AKAP4 and AKAP8 Additionally, AKAP4 and AKAP3 from DFS sperm retained the ability to bind the regulatory subunit of protein kinase A. Localization at the light and electron microscopic level s showed that AKAP3 and AKAP4 localized correctly to the FS of the amorphou s flagellum in DFS sperm. Partial sequence analysis of the AKAP4 and AKAP3 genes in patients with DFS did not identity any significant alterations in potential AKAP4/AKAP3 binding regions, suggesting that the two proteins int eract normally in DFS sperm. Our results did not find evidence to support t he hypothesis that mutations in either gene are responsible for DFS in huma ns.