Biology subjects

Brukman, N. G.

Publications and source records attributed to Brukman, N. G..

3 recordsLinked to original sources

bioRxiv2023

Sperm induction of somatic cell-cell fusion as a novel functional test

The fusion of mammalian gametes requires the interaction between IZUMO1 on the sperm and JUNO on the oocyte. We have recently shown that ectopic expression of mouse IZUMO1 induces cell-cell fusion and that sperm can fuse to fibroblasts expressing JUNO. Here, we found that the incubation of mouse sperm with hamster fibroblasts or human epithelial cells in culture induces the fusion between these somatic cells and formation of syncytia, a pattern previously observed with some animal viruses. This sperm-induced cell-cell fusion requires a species-matching JUNO on both fusing cells, can be blocked by an antibody against IZUMO1, and does not rely on the synthesis of new proteins. The fusion is dependent on the sperms fusogenic capacity, making this a reliable, fast and simple method for predicting sperm function during the diagnosis of male infertility. HighlightsO_LISperm induces viral-like fusion of somatic cells expressing JUNO C_LIO_LIWe developed a new technique to determine the fertilization potential of sperm C_LIO_LIThe test measures the capacity of sperm to induce somatic cell fusion C_LIO_LIThe degree of somatic cell fusion correlates with the fertilizing ability of sperm C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=141 SRC="FIGDIR/small/549574v2_ufig1.gif" ALT="Figure 1"> View larger version (28K): org.highwire.dtl.DTLVardef@7f1d7corg.highwire.dtl.DTLVardef@168d0c3org.highwire.dtl.DTLVardef@61e845org.highwire.dtl.DTLVardef@1d83b72_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2022

IZUMO1 is a sperm fusogen

Mammalian sperm-egg adhesion depends on the trans-interaction between the sperm-specific type I glycoprotein IZUMO1 and its oocyte-specific GPI-anchored receptor JUNO. However, the mechanisms and proteins (fusogens) which mediate the following step of gamete fusion remain unknown. Using live imaging and content mixing assays in a heterologous system and structure-guided mutagenesis, we unveil an unexpected function for IZUMO1 in cell-to-cell fusion. We show that IZUMO1 alone is sufficient to induce fusion, and that this ability is retained in a mutant unable to bind JUNO. On the other hand, a triple mutation in exposed aromatic residues prevents this fusogenic activity without impairing JUNO interaction. Our findings suggest a second, crucial function for IZUMO1 as a unilateral mouse gamete fusogen. HighlightsO_LIIZUMO1 expression in somatic cells in culture induces cell-to-cell fusion C_LIO_LIThe fusogenic activity of IZUMO1 is unilateral C_LIO_LICell fusion is independent of the binding of IZUMO1 to JUNO C_LIO_LIIZUMO1-mediated cell merger depends on its transmembrane domain, and three solvent-exposed aromatic residues C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/478669v2_ufig1.gif" ALT="Figure 1"> View larger version (44K): org.highwire.dtl.DTLVardef@1f06f47org.highwire.dtl.DTLVardef@19d5adorg.highwire.dtl.DTLVardef@1b8d6eorg.highwire.dtl.DTLVardef@e23e26_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2021

Archaeal origins of gamete fusion

Sexual reproduction consists of genome reduction by meiosis and subsequent gamete fusion. Presence of meiotic genes in prokaryotes suggests that DNA repair mechanisms evolved toward meiotic recombination; however, fusogenic proteins resembling those found in eukaryotes were not identified in prokaryotes. Here, we identify archaeal proteins that are homologs of fusexins, a superfamily of fusogens that mediate eukaryotic gamete and somatic cell fusion, as well as virus entry. The crystal structure of a trimeric archaeal Fusexin1 reveals novel features such as a six-helix bundle and an additional globular domain. Ectopically expressed Fusexin1 can fuse mammalian cells, and this process involves the additional domain and a conserved fusion loop. Archaeal fusexin genes exist within integrated mobile elements, potentially linking ancient archaeal gene exchanges and eukaryotic sex. One-Sentence SummaryCell membrane fusion proteins of viruses and eukaryotes are also present in archaea.

evolutionary biology↗