TMEM95 is a sperm membrane protein essential for mammalian fertilization

• Published in: eLife Vol. 9
• Main Authors: Lamas-Toranzo, Ismael, Hamze, Julieta G, Bianchi, Enrica, Fernández-Fuertes, Beatriz, Pérez-Cerezales, Serafín, Laguna-Barraza, Ricardo, Fernández-González, Raúl, Lonergan, Pat, Gutiérrez-Adán, Alfonso, Wright, Gavin J, Jiménez-Movilla, María, Bermejo-Álvarez, Pablo
• Format: Journal Article
• Language: English
• Published: England eLife Science Publications, Ltd 02-06-2020; eLife Sciences Publications Ltd; eLife Sciences Publications, Ltd
• Subjects: Ablation; Amino acids; Animals; Antibodies; Cell Biology; Cell Membrane - metabolism; CRISPR; Developmental Biology; Embryos; Female; Fertilization; Gene Editing; Genes, Reporter; Genomes; Immunoglobulins - genetics; Immunoglobulins - metabolism; Infertility; Infertility, Male - genetics; IZUMO; JUNO; Localization; Male; Mammals; Membrane fusion; Membrane proteins; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Motility; Mutation; Peptides; Prostate; Proteins; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; reproduction; Seminal Plasma Proteins - genetics; Seminal Plasma Proteins - metabolism; Sexual reproduction; Sperm; Sperm-Ovum Interactions - genetics; Spermatozoa - physiology; Zona pellucida; mouse; cell biology; fertilization; developmental biology; IZUMO; JUNO; reproduction
• ISSN: 2050-084X; 2050-084X
• DOI: 10.7554/elife.53913

The fusion of gamete membranes during fertilization is an essential process for sexual reproduction. Despite its importance, only three proteins are known to be indispensable for sperm-egg membrane fusion: the sperm proteins IZUMO1 and SPACA6, and the egg protein JUNO. Here we demonstrate that another sperm protein, TMEM95, is necessary for sperm-egg interaction. TMEM95 ablation in mice caused complete male-specific infertility. Sperm lacking this protein were morphologically normal exhibited normal motility, and could penetrate the zona pellucida and bind to the oolemma. However, once bound to the oolemma, TMEM95-deficient sperm were unable to fuse with the egg membrane or penetrate into the ooplasm, and fertilization could only be achieved by mechanical injection of one sperm into the ooplasm, thereby bypassing membrane fusion. These data demonstrate that TMEM95 is essential for mammalian fertilization.