Open AccessA noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis
Author(s) -
Yike Yin,
Shiyu Cao,
Huancheng Fu,
Xueying Fan,
Jingfei Xiong,
Qingqing Huang,
Yu Liu,
Kun Xie,
TieGang Meng,
Yuliang Liu,
Dan Tang,
Tingting Yang,
Biao Dong,
Shiqian Qi,
Ling Nie,
Huiyuan Zhang,
Hongbo Hu,
Wei Xu,
Fuping Li,
Lunzhi Dai,
QingYuan Sun,
Zhonghan Li
Publication year - 2020
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2005533117
Subject(s) - biology , germ cell , microbiology and biotechnology , spermatogenesis , germline , cellular differentiation , somatic cell , genetics , gene , endocrinology
Significance NOD-like receptors (NLRs) are traditionally recognized as key surveillance pattern recognition receptors (PRRs) during innate immune regulation. Several NLRs exhibit highly restricted expression in mammalian germline, where their physiological functions are largely unknown. Here we report that Nlrp14, an NLR specifically expressed in testis and ovary, plays a critical role in regulating germ cell differentiation and reproduction. Nlrp14 deficiency led to decreased primordial germ cell-like cell (PGCLC) differentiation in vitro and reproduction failure in both male and female mice in vivo. In the male mice, Nlrp14 knockout strongly compromised differentiation of spermatogonial stem cells and meiosis. Mechanistically, NLRP14 protected HSPA2 from proteasome-mediated degradation by recruiting BAG2, loss of which was further confirmed in a human mutation associated with male sterility.