title: An X-linked gene encodes a major human sperm fibrous sheath protein, hAKAP82. Genomic organization, protein kinase A-RII binding, and distribution of the precursor in the sperm tail.
abstract: Mammalian sperm motility is regulated by a cascade of cAMP-dependent protein phosphorylation events mediated by protein kinase A. A-kinase anchor proteins (AKAPs) direct protein kinase A activity by tethering the enzyme near its physiological substrates. We have characterized a major human sperm fibrous sheath AKAP, hAKAP82, and its precursor, pro-hAKAP82, the homologues of the mouse fibrous sheath proteins mAKAP82 and 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 cleavage 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-hAKAP82 was processed to hAKAP82 in human sperm. Although pro-mAKAP82 localizes only to the proximal portion of the principal piece of the flagellum, pro-hAKAP82 localized to the entire length of the principal piece. The pro-hAKAP82 gene mapped to human chromosome Xp11.2, indicating that defects in this gene are maternally inherited. These studies suggest several roles for hAKAP82 in sperm motility, including the regulation of signal transduction pathways.
authors.affiliation: Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Turner
authors.forename: L R
authors.initials: LR
authors.lastname: Johnson
authors.forename: L
authors.initials: L
authors.lastname: Haig-Ladewig
authors.forename: G L
authors.initials: GL
authors.lastname: Gerton
authors.forename: S B
authors.initials: SB
authors.lastname: Moss
mesh_terms: D054758:A Kinase Anchor Proteins; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002874:Chromosome Mapping; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D005260:Female; D015723:Gene Library; D018392:Genomic Imprinting; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011498:Protein Precursors / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D029589:Seminal Plasma Proteins; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013082:Sperm Tail / Q000378:metabolism* / Q000648:ultrastructure; D013737:Testis / Q000378:metabolism; D014960:X Chromosome
chemical_list: D054758:A Kinase Anchor Proteins; C485480:AKAP4 protein, human; C485479:Akap4 protein, mouse; D046911:Macromolecular Substances; D011498:Protein Precursors; D011506:Proteins; D029589:Seminal Plasma Proteins; C116030:pro-AKAP82 protein, mammalian; D017868:Cyclic AMP-Dependent Protein Kinases