Coxsackievirus and adenovirus receptor (CAR) is expressed in male germ cells and forms a complex with the differentiation factor JAM-C in mouse testis

Coxsackievirus and adenovirus receptor (CAR) is expressed in male germ cells and forms a complex with the differentiation factor JAM-C in mouse testis
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DOI:
10.1016/j.yexcr.2005.11.030
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发表时间:
2006-04-01
影响因子:
3.7
通讯作者:
Sollerbrant, K
Sollerbrant, K
中科院分区:
医学3区
文献类型:
--
作者:
Mirza, M;Hreinsson, J;Sollerbrant, K

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柯萨奇病毒和腺病毒受体(CAR)是一种跨膜蛋白,对病毒与靶细胞的结合很重要。使用RT-PCR,Western分析,GST pull-down测定和间接免疫荧光,表明CAR在小鼠,大鼠和人的雄性生殖细胞中表达。在睾丸中的圆形精子细胞以及纯化的成熟精子中检测到CAR。CAR的两种膜结合亚型在精子顶体区域占据不同的亚细胞位点。CAR暴露在顶体反应的细胞表面,而不是顶体完整的细胞表面。两个CAR结合蛋白属于ligand-of-numprotein-X(LNX)家族,在精子中也占据了不同的区域。最后,免疫共沉淀实验证明了CAR和JAM-C之间的相互作用,JAM-C是精子细胞分化所需的蛋白质。总之,这些发现暗示了CAR在男性生育中的功能。这些结果还表明,精子中的CAR是基于腺病毒的基因治疗载体无法接近的,因此生殖系感染的风险很低。
The coxsackievirus and adenovirus receptor (CAR) is a transmembrane protein important for viral binding to target cells. Using RT-PCR, Western analysis, GST pull-down assay and indirect immunofluorescence, it was shown that CAR is expressed in male germ cells from mice, rats, and humans. CAR was detected in round spermatids in the testis as well as in purified, mature spermatozoa. The two membrane-bound isoforms of CAR occupied different subcellular sites in the acrosomal region of the spermatozoa. CAR was exposed on the surface of acrosome-reacted, but not acrosome-intact cells. Two CAR-binding proteins belonging to the ligand-of-numb protein-X (LNX) family also occupied distinct regions in spermatozoa. Finally, co-immunoprecipitation experiments demonstrated an interaction between CAR and JAM-C, a protein required for spermatid differentiation. Together, these findings imply a function for CAR in male fertility. The results also suggest that CAR in spermatozoa is inaccessible to adenovirus-based gene therapy vectors, and that the risk of germ line infection therefore is low.