Changes in intracellular distribution and activity of protein phosphatase PP1γ2 and its regulating proteins in spermatozoa lacking AKAP4
Changes in intracellular distribution and activity of protein phosphatase PP1γ2 and its regulating proteins in spermatozoa lacking AKAP4
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DOI：
10.1095/biolreprod.104.034140
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发表时间：
2005-02-01
影响因子：
3.6
通讯作者：
Vijayaraghavan, S
中科院分区：
文献类型：
--
作者：
Huang, ZH;Somanath, PR;Vijayaraghavan, S
第二信使cAMP通过cAMP依赖性激酶（PKA，正式称为PRKACA）介导其在精子中的细胞内效应。PKA在精子中的细胞内组织是通过与A激酶锚定蛋白（AKAP）的结合来控制的。AKAP 4（A激酶[PRKA]锚蛋白4;也称为纤维鞘组分1或AKAP 82）是精子特异性的，并且是精子鞭毛的主要片段的主要纤维鞘蛋白。据推测，AKAP 4招募PKA到纤维鞘，并促进局部磷酸化以调节鞭毛功能。它还被提议作为信号蛋白和参与代谢的蛋白的支架蛋白。Akap 4基因敲除小鼠由于缺乏精子活力而不育。突变小鼠精子的纤维鞘被破坏。本文以A4基因敲除小鼠为研究对象，研究了纤维鞘破坏对PKA催化和调节亚基、精子鞭毛蛋白PP 1 γ 2的存在、亚细胞分布和/或活性变化的影响（蛋白磷酸酶1，催化亚基，γ亚型，正式名称为PPP 1CC），GSK-3（糖原合成酶激酶-3）、SP17（精子自身抗原蛋白17，正式称为SPA 17）和其他信号蛋白。PP 1 γ 2、GSK-3、hsp 90的存在和亚细胞分布无变化（热休克蛋白1，α，正式名称为HSPCA），sds 22（蛋白磷酸酶1，调节[抑制剂]亚基7，正式名称为PPP 1 R7），14-3-3蛋白（酪氨酸3-单加氧酶/色氨酸5-单加氧酶激活蛋白）和PKB（胸腺瘤病毒原癌基因，也称为AKT）。然而，PKA催化亚基和调节亚基，PI 3-激酶（磷脂酰肌醇3-激酶），和SP17的亚细胞分布在突变小鼠中被破坏。此外，突变体精子中PP 1 γ 2的活性和磷酸化水平与野生型精子相比有显著变化。这些研究已经确定了纤维鞘在调节关键信号传导酶的活性和功能方面的潜在重要的新作用。
The second messenger cAMP mediates its intracellular effects in spermatozoa through cAMP-dependent kinase (PKA, formally known as PRKACA). The intracellular organization of PKA in spermatozoa is controlled through its association with A-kinase-anchoring proteins (AKAPs). AKAP4 (A kinase [PRKA] anchor protein 4; also called fibrous sheath component 1 or AKAP 82) is sperm specific and the major fibrous sheath protein of the principal piece of the sperm flagellum. Presumably, AKAP4 recruits PKA to the fibrous sheath and facilitates local phosphorylation to regulate flagellar function. It is also proposed to act as a scaffolding protein for signaling proteins and proteins involved in metabolism. Akap4 gene knockout mice are infertile due to the lack of sperm motility. The fibrous sheath is disrupted in spermatozoa from mutant mice. In this article, we used A 4 gene knockout mice to study the effect of fibrous sheath disruption on the presence, subcellular distribution, and/or activity changes of PKA catalytic and regulatory subunits, sperm flagellum proteins PP1gamma2 (protein phosphatase 1, catalytic subunit, gamma isoform, formally known as PPP1CC), GSK-3 (glycogen synthase kinase-3), SP17 (sperm autoantigenic protein 17, formally known as SPA17), and other signaling proteins. There were no changes in the presence and subcellular distribution for PP1gamma2, GSK-3, hsp90 (heat shock protein 1, alpha, formally known as HSPCA), sds22 (protein phosphatase 1, regulatory [inhibitor] subunit 7, formally known as PPP1R7), 14-3-3 protein (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein), and PKB (thymoma viral proto-oncogene, also known as AKT) in mutant mice. However, the subcellular distributions for PKA catalytic subunit and regulatory subunits, PI 3-kinase (phosphatidylinositol 3-kinase), and SP17 were disrupted in mutant mice. Furthermore, there was a significant change in the activity and phosphorylation of PP1gamma2 in mutant compared with wild-type spermatozoa. These studies have identified potentially significant new roles for the fibrous sheath in regulating the activity and function of key signaling enzymes.