National Demonstration Center for Experimental Basic Medical Education, and State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China.
State Key Laboratory of Medical Molecular Biology, and Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, No. 5, Dongdan Santiao, Dongcheng District, Beijing, 100005, China.
Cell Tissue Res. 2023 Jun;392(3):811-826. doi: 10.1007/s00441-023-03759-5. Epub 2023 Mar 6.
The adhesion protein nectin-like molecule 2 (NECL2) is involved in spermatogenesis and participates in the connections between Sertoli cells and germ cells. Necl2 deficiency leads to infertility in male mice. We found that NECL2 is relatively highly expressed on the cell membranes of preleptotene spermatocytes. It is known that preleptotene spermatocytes pass through the blood-testis barrier (BTB) from the base of the seminiferous tubules to the lumen to complete meiosis. We hypothesized that the NECL2 protein on the surfaces of preleptotene spermatocytes has an effect on the BTB when crossing the barrier. Our results showed that Necl2 deficiency caused the levels of proteins in the BTB to be abnormal, such as those of Claudin 3, claudin 11, and Connexin43. NECL2 interacted and colocalized with adhesion proteins forming the BTB, such as Connexin43, Occludin, and N-cadherin. NECL2 regulated BTB dynamics when preleptotene spermatocytes passed through the barrier, and Necl2 deficiency caused BTB damage. Necl2 deletion significantly affected the testicular transcriptome, especially the expression of spermatogenesis-related genes. These results suggest that before meiosis and spermatid development occur, BTB dynamics regulated by NECL2 are necessary for spermatogenesis.
黏附蛋白 nectin-like 分子 2（NECL2）参与精子发生，并参与支持细胞和生殖细胞之间的连接。Necl2 缺失导致雄性小鼠不育。我们发现，NECL2 在精原细胞细线期前细胞的细胞膜上相对高表达。已知精原细胞细线期前细胞从生精小管的基底穿过血睾屏障（BTB）到管腔，以完成减数分裂。我们假设穿过屏障时，精原细胞细线期前细胞表面的 NECL2 蛋白对 BTB 有影响。我们的结果表明，Necl2 缺失导致 BTB 中的蛋白水平异常，如 Claudin3、Claudin11 和 Connexin43。NECL2 与形成 BTB 的黏附蛋白相互作用并共定位，如 Connexin43、Occludin 和 N-钙黏蛋白。NECL2 调节精原细胞细线期前穿过屏障时的 BTB 动力学，Necl2 缺失导致 BTB 损伤。Necl2 缺失显著影响睾丸转录组，特别是与精子发生相关基因的表达。这些结果表明，在减数分裂和精子细胞发育之前，NECL2 调节的 BTB 动力学对于精子发生是必要的。
