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

• Autor: Lu, Yonggang ; Shimada, Kentaro ; Tang, Shaogeng ; Zhang, Jingjing ; Ogawa, Yo ; Noda, Taichi ; Shibuya, Hiroki ; Ikawa, Masahito
• Assuntos: Ablation ; Acrosome ; Acrosome - metabolism ; Animals ; Biological Sciences ; Biosynthesis ; Catalytic subunits ; Cell Biology ; Cellbiologi ; Eggs ; Endoplasmic reticulum ; Fertilization ; genetics ; Glycosylation ; Golgi apparatus ; Isomerization ; Knockout ; Male ; Mammals ; Mammals - metabolism ; Membrane Proteins ; Membrane Proteins - genetics ; Membrane Proteins - metabolism ; Membranes ; metabolism ; Mice ; Mice, Knockout ; Oligosaccharyltransferase ; Ovum ; Ovum - metabolism ; Proteins ; Semen ; Semen - metabolism ; Seminal Plasma Proteins ; Seminal Plasma Proteins - metabolism ; Sperm ; Sperm-Ovum Interactions ; Spermatids ; Spermatozoa ; Spermatozoa - metabolism ; Spermiogenesis ; Ubiquitination
• É parte de: Proceedings of the National Academy of Sciences - PNAS, 2023-02, Vol.120 (8), p.e2207263120-e2207263120
• Notas: ObjectType-Article-1
  SourceType-Scholarly Journals-1
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  Edited by Laurinda Jaffe, UConn Health, Farmington, CT; received April 27, 2022; accepted January 17, 2023
  
• Descrição: 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 knockout male mice are severely subfertile and their spermatozoa do not fuse with eggs. 1700029I15Rik is a type-II transmembrane protein expressed in early round spermatids but not in mature spermatozoa. It interacts with proteins involved in -linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. The ablation of destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for -glycosylation. The knockout testes exhibit normal expression of sperm plasma membrane proteins, but decreased abundance of multiple acrosomal membrane proteins involved in fertilization. The knockout sperm show upregulated chaperones related to ER-associated degradation (ERAD) and elevated protein ubiquitination; strikingly, SPACA6 becomes undetectable. Our results support for a specific, 1700029I15Rik-mediated pathway underpinning the biosynthesis of acrosomal membrane proteins during spermiogenesis.
  
• Editor: United States: National Academy of Sciences
  
• Idioma: Inglês