1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm–egg interaction

• DOI: 10.1073/pnas.2207263120
• Publication Date: 2023-02-14T18:54:36Z
• Authors: Yonggang Lu; Kentaro Shimada; Shaogeng Tang; Jingjing Zhang; Yo Ogawa; Taichi Noda; Hiroki Shibuya; Masahito Ikawa
• Keywords: Spermiogenesis; Endoplasmic-reticulum-associated protein degradation

Sperm acrosomal membrane proteins, such as Izumo sperm–egg fusion 1 (IZUMO1) and sperm acrosome-associated 6 (SPACA6), play essential roles in mammalian gamete binding or fusion. How their biosynthesis is regulated during spermiogenesis has largely remained elusive. Here, we show that 1700029I15Rik knockout male mice are severely subfertile spermatozoa do not fuse with eggs. a type-II transmembrane protein expressed early round spermatids but mature spermatozoa. It interacts proteins involved N -linked glycosylation, disulfide isomerization, endoplasmic reticulum (ER)–Golgi trafficking, suggesting potential role nascent processing. The ablation of destabilizes non-catalytic subunits the oligosaccharyltransferase (OST) complex pivotal for -glycosylation. testes exhibit normal expression plasma decreased abundance multiple fertilization. upregulated chaperones related to ER-associated degradation (ERAD) elevated ubiquitination; strikingly, SPACA6 becomes undetectable. Our results support specific, 1700029I15Rik-mediated pathway underpinning spermiogenesis.