Mice lacking raf kinase inhibitor protein-1 (RKIP-1) have altered sperm capacitation and reduced reproduction rates with a normal response to testicular injury
Mice lacking raf kinase inhibitor protein-1 (RKIP-1) have altered sperm capacitation and reduced reproduction rates with a normal response to testicular injury
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DOI：
10.2164/jandrol.107.002964
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发表时间：
2007-11-01
影响因子：
--
通讯作者：
Klysik, Jan
中科院分区：
文献类型：
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作者：
Moffit, Jeffrey S.;Boekelheide, Kim;Klysik, Jan
Raf激酶抑制剂蛋白-1 （RKIP-1）属于磷脂酰乙醇胺结合蛋白家族（PEBP），在整个进化过程中高度保守，在哺乳动物组织中广泛表达。RKIP-1是细胞外信号调节激酶（ERK）、核因子κ B （nf - κ B）和G蛋白偶联受体（GPCR）信号级联的调节剂，是许多生理过程和疾病状态包括转移的一个因素。睾丸生殖细胞在精子发生过程中也表达高水平的RKIP mRNA，特别是从后期粗线期精子细胞到第15步长形精子细胞。因此，我们比较了野生型和RKIP-1（-/-）小鼠精子发生对损伤的敏感性。与肿瘤抑制因子如p53不同，RKIP-/-和野生型小鼠对x射线照射下的生殖细胞毒性同样敏感，在5gy照射后9小时，通过末端脱氧核苷酸转移酶生物素-脱氧尿苷三磷酸（dUTP） nick末端标记（TUNEL）阳性评估，在0.5 Gy照射后15.5天，睾丸精细胞头计数评估。最近的研究结果也表明RKIP是精子上的失能因子受体。目前的研究表明，与野生型小鼠相比，rkip缺陷小鼠的精子具有早熟能力。交配实验数据表明，RKIP-1（-/-）雄性小鼠与杂合或RKIP-1（-/-）雌性小鼠的杂交繁殖率降低。此外，附睾精子的RKIP免疫定位支持在附睾运输过程中，RKIP蛋白通过细胞质液滴从生殖细胞细胞质转移到精子。总的来说，这些研究表明RKIP在生殖中作为能化的调节剂发挥重要作用，但在睾丸损伤的调节中没有作用。
Raf kinase inhibitor protein-1 (RKIP-1) belongs to the phosphatidyl ethanolamine-binding family of proteins (PEBP), which are highly conserved throughout evolution and widely expressed in tissues of mammalian organisms. RKIP-1 is a modulator of extracellular signal-regulated kinase (ERK), nuclear factor-kappa B (NF-kappa B), and G protein coupled receptor (GPCR) signaling cascades and is implicated as a factor in numerous physiological processes and disease states including metastasis. Testicular germ cells also express high levels of RKIP mRNA during spermatogenesis, particularly from late pachytene spermatocytes through step 15 elongate spermatids. Therefore, the sensitivity of spermatogenesis to injury was compared in wild-type and RKIP-1(-/-) mice. Unlike what has been described with tumor suppressors such as p53, RKIP-/- and wild-type mice were equally sensitive to germ cell toxicity by x-irradiation as assessed by terminal deoxynucleotidyl transferase biotin-deoxyuridine triphosphate (dUTP) nick end labeling (TUNEL) positivity 9 hours after a 5 Gy exposure and testicular spermatid head counts 15.5 days after 0.5 Gy exposure. Recent findings also indicate that RKIP is a decapacitation factor receptor on sperm. The present study demonstrates that sperm from RKIP-deficient mice are precociously capacitated compared with their wild-type counterparts. Data from mating experiments indicate decreased reproduction rates between crosses of RKIP-1(-/-) male mice and either heterozygous or RKIP-1(-/-) females. Furthermore, RKIP immunolocalization of epididymal sperm supports transfer of the protein from germ cell cytoplasm to the sperm via the cytoplasmic droplet during epididymal transport. Overall, these studies indicate an important role for RKIP in reproduction as a modulator of capacitation but not in the regulation of testicular injury.