RRC ID 76643
Author Lu Y, Shimada K, Tang S, Zhang J, Ogawa Y, Noda T, Shibuya H, Ikawa M.
Title 1700029I15Rik orchestrates the biosynthesis of acrosomal membrane proteins required for sperm-egg interaction.
Journal Proc Natl Acad Sci U S A
Abstract 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 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 N-linked glycosylation, disulfide isomerization, and endoplasmic reticulum (ER)-Golgi trafficking, suggesting a potential role in nascent protein processing. The ablation of 1700029I15Rik destabilizes non-catalytic subunits of the oligosaccharyltransferase (OST) complex that are pivotal for N-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.
Volume 120(8)
Pages e2207263120
Published 2023-2-21
DOI 10.1073/pnas.2207263120
PMID 36787362
PMC PMC9974436
MeSH Acrosome* / metabolism Animals Male Mammals / metabolism Membrane Proteins* / genetics Membrane Proteins* / metabolism Mice Mice, Knockout Ovum / metabolism Semen / metabolism Seminal Plasma Proteins / metabolism Sperm-Ovum Interactions Spermatozoa / metabolism
IF 9.412
DNA material pCAG-1700029I15Rik-3×FLAG (RDB19976)