| Literature DB >> 32499443 |
Daiji Kiyozumi1,2, Taichi Noda1,2, Ryo Yamaguchi2,3, Tomohiro Tobita2,4, Takafumi Matsumura2,3, Kentaro Shimada2,3, Mayo Kodani2,3, Takashi Kohda5, Yoshitaka Fujihara1,2, Manabu Ozawa6, Zhifeng Yu7, Gabriella Miklossy7, Kurt M Bohren7, Masato Horie8, Masaru Okabe1,2,3, Martin M Matzuk9,10,11,12, Masahito Ikawa13,2,3,4,6.
Abstract
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.Entities:
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Year: 2020 PMID： 32499443 PMCID： PMC7396227 DOI： 10.1126/science.aay5134
Source DB: PubMed Journal: Science ISSN： 0036-8075 Impact factor: 47.728