Turner R M, Johnson L R, Haig-Ladewig L, Gerton G L, Moss S B
Center for Research on Reproduction and Women's Health, Department of Obstetrics and Gynecology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
J Biol Chem. 1998 Nov 27;273(48):32135-41. doi: 10.1074/jbc.273.48.32135.
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.
哺乳动物精子的运动受蛋白激酶A介导的一系列环磷酸腺苷（cAMP）依赖性蛋白磷酸化事件调控。A激酶锚定蛋白（AKAPs）通过将该酶拴系在其生理底物附近来指导蛋白激酶A的活性。我们已对一种主要的人类精子纤维鞘AKAP，即hAKAP82及其前体pro-hAKAP82进行了表征，它们分别是小鼠纤维鞘蛋白mAKAP82和pro-mAKAP82的同源物。pro-hAKAP82的cDNA序列与小鼠序列高度同源，且pro-hAKAP82蛋白的功能结构域、蛋白激酶A结合位点以及pro-hAKAP82/hAKAP82的切割位点与小鼠蛋白的相同。已确定了小鼠pro-AKAP82的基因组结构。小鼠和人类的pro-AKAP82基因均发生了可变剪接，产生了至少两种不同的转录本以及可能两种不同的蛋白质。与pro-mAKAP82相比，人类精子中加工成hAKAP82的pro-hAKAP82要少得多。尽管pro-mAKAP82仅定位于鞭毛主段的近端部分，但pro-hAKAP82定位于主段的全长。pro-hAKAP82基因定位于人类X染色体p11.2，这表明该基因的缺陷是母系遗传的。这些研究表明hAKAP82在精子运动中具有多种作用，包括对信号转导通路的调控。
