NELL2媒介によるOVCH2によるルミクリンシグナル伝達が男性の生育に必要である

Daiji Kiyozumi^1,2, Taichi Noda^1,2, Ryo Yamaguchi^2,3

¹Immunology Frontier Research Center, Osaka University, Suita, Osaka 5650871, Japan.

Science (New York, N.Y.)

|June 6, 2020

まとめ

神経表皮成長因子類似2 (NELL2) は,男性生育に決定的な,最初に特定されたルミクリン因子である. 精巣に由来するこのタンパク質は ROS1を通じて精子の成熟経路を調節する信号を送ります

科学分野:

生殖生物学
分子内分泌学
細胞シグナリング

背景:

ルミクリン系は,丸因子が男性生殖器系に影響を与える,提案された信号経路である.
以前は,特定のルミクリン因子やそのメカニズムが特定されていなかった.

研究の目的:

男性の生殖シグナルに関わる最初のルミクリン因子を特定する.
この因子が精子の成熟を調節する分子メカニズムを解明する.

主な方法:

NELL2の機能を評価するためにノックアウトマウスモデルを使用した.
NELL2とその受容体間のタンパク質相互作用を調査した.
エピディジマ・プロテアゼと精子の機能に対する下流効果を分析した.

主要な成果:

ニューラル表皮成長因子2 (NELL2) を丸由来ルミクリン因子として特定した.
NELL2は孤児受容体チロシンキナーゼROS1と結合し, epididymal初期セグメントの分化を媒介する.
ネル2のノックアウトマウスは不妊で,OVCH2- ADAM3の処理が妨げられたため精子の成熟が低下した.

結論:

NELL2-ROS1シグナリングを含む最初の機能的なルミクリンシステムを確立しました.
この経路の重要な役割は,先頭葉のプロテアゼを介して精子の受精能力を調節することを示した.
このNELL2-ROS1-OVCH2-ADAM3軸は男性の生育に不可欠です.

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