Ablation of the scaffold protein JLP causes reduced fertility in male mice
Ablation of the scaffold protein JLP causes reduced fertility in male mice
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DOI：
10.1007/s11248-008-9191-6
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发表时间：
2008-12-01
影响因子：
3
通讯作者：
Yoshioka, Katsuji
中科院分区：
文献类型：
--
作者：
Iwanaga, Asuka;Wang, Guangmin;Yoshioka, Katsuji
丝裂原活化蛋白激酶（MAPK）信号传导模块的特异性和有效的活化至少部分地由支架蛋白介导。c-Jun NH（2）-末端激酶（JNK）相关亮氨酸拉链蛋白（JLP）被鉴定为JNK和p38 MAPK信号传导模块的支架蛋白。JLP在体外几乎无处不在地表达，并参与细胞内信号传导途径，如G（α 13）和Cdo介导的途径。然而，到目前为止，JLP的表达还没有被详细分析，其生理功能也没有得到很好的理解。本文研究了JLP在小鼠睾丸发育过程中的表达。在检查的组织中，JLP在睾丸中最强，在细长的精子细胞中染色最强烈。由于本研究中使用的抗JLP抗体可以识别JLP和精子相关抗原9（SPAG 9），JLP的剪接变体已在灵长类动物中广泛研究，我们还研究了其在猕猴睾丸样品中的表达。我们的结果表明，在小鼠和灵长类动物睾丸中，表达水平最高的亚型是JLP，而不是SPAG 9。我们还通过破坏小鼠Jlp基因来研究JLP的功能，发现雄性纯合子生育力低下。总之，这些观察结果可能表明，JLP在睾丸发育过程中起着重要作用，特别是在功能正常的精子的生产。
The specific and efficient activation of mitogen-activated protein kinase (MAPK) signaling modules is mediated, at least in part, by scaffold proteins. c-Jun NH(2)-terminal kinase (JNK)-associated leucine zipper protein (JLP) was identified as a scaffold protein for JNK and p38 MAPK signaling modules. JLP is expressed nearly ubiquitously and is involved in intracellular signaling pathways, such as the G(alpha 13) and Cdo-mediated pathway, in vitro. To date, however, JLP expression has not been analyzed in detail, nor are its physiological functions well understood. Here we investigated the expression of JLP in the mouse testis during development. Of the tissues examined, JLP was strongest in the testis, with the most intense staining in the elongated spermatids. Since the anti-JLP antibody used in this study can recognize both JLP and sperm-associated antigen 9 (SPAG9), a splice variant of JLP that has been studied extensively in primates, we also examined its expression in macaque testis samples. Our results indicated that in mouse and primate testis, the isoform expressed at the highest level was JLP, not SPAG9. We also investigated the function of JLP by disrupting the Jlp gene in mice, and found that the male homozygotes were subfertile. Taken together, these observations may suggest that JLP plays an important role in testis during development, especially in the production of functionally normal spermatozoa.