AN X-LINKED GENE ENCODES A MAJOR HUMAN SPERM FIBROUS SHEATH PROTEIN, HAKAP82

Mammalian sperm motility is regulated by a cascade of cAMP-dependent p rotein phosphorylation events mediated by protein kinase A. A-kinase a nchor proteins (AKAPs) direct protein kinase A activity by tethering t he enzyme near its physiological substrates, We have characterized a m ajor human sperm fibrous sheath AKAP, hAKAP82, and its precursor, pro- hAKAP82, the homologues of the mouse fibrous sheath proteins mAKAP82 a nd pro-mAKAP82. The cDNA sequence of pro-hAKAP82 was highly homologous to the mouse sequence, and the functional domains of the pro-hAKAP82 protein, the protein kinase A binding, and the pro-hAKAP82/hAKAP82 cle avage sites were identical to those of the mouse protein. The genomic organization of mouse pro-AKAP82 was determined. Alternative splicing occurred in both the mouse and human pro-AKAP82 genes that resulted in at least two distinct transcripts and possibly two different proteins . Compared with pro-mAKAP82, considerably less pro-hAKAP8a was process ed to hAKAP82 in human sperm. Although pro-mAKAP82 localizes only to t he proximal portion of the principal piece of the flagellum, pro-hAKAP 82 localized to the entire length of the principal piece. The pro-hAKA P82 gene mapped to human chromosome Xp11.2, indicating that defects in this gene are maternally inherited, These studies suggest several rol es for hAKAP82 in sperm motility, including the regulation of signal t ransduction pathways.