Science (New York, N.Y.) · 2020
NELL2-mediated lumicrine signaling through OVCH2 is required for male fertility.
СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Kiyozumi Daiji, Noda Taichi, Yamaguchi Ryo, Tobita Tomohiro, Matsumura Takafumi, Shimada Kentaro, Kodani Mayo, Kohda Takashi, Fujihara Yoshitaka, Ozawa Manabu, Yu Zhifeng, Miklossy Gabriella, Bohren Kurt M, Horie Masato, Okabe Masaru, Matzuk Martin M, Ikawa Masahito
Аннотация
The lumicrine system is a postulated signaling system in which testis-derived (upstream) secreted factors enter the male reproductive tract to regulate epididymal (downstream) pathways required for sperm maturation. Until now, no lumicrine factors have been identified. We demonstrate that a testicular germ-cell-secreted epidermal growth factor-like protein, neural epidermal growth factor-like-like 2 (NELL2), specifically binds to an orphan receptor tyrosine kinase, c-ros oncogene 1 (ROS1), and mediates the differentiation of the initial segment (IS) of the caput epididymis. Male mice in which Nell2 had been knocked out were infertile. The IS-specific secreted proteases, ovochymase 2 (OVCH2) and A disintegrin and metallopeptidase 28 (ADAM28), were expressed upon IS maturation, and OVCH2 was required for processing of the sperm surface protein ADAM3, which is required for sperm fertilizing ability. This work identifies a lumicrine system essential for testis-epididymis-spermatozoa (NELL2-ROS1-OVCH2-ADAM3) signaling and male fertility.