A noncanonical role of NOD-like receptor NLRP14 in PGCLC differentiation and spermatogenesis

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Abstract
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.
Funding Information
  • National Key Research and Development Program of China (2017YFA0104801)
  • National Science Foundation of China (31900900)
  • National Science Foundation of China (31401262)
  • China Postdoctoral Science Foundation (2018M633361)
  • Fundamental Research Funds for the Central Universities (SCU2019D013)

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