scholarly journals Fusexins, HAP2/GCS1 and Evolution of Gamete Fusion

2022 ◽  
Vol 9 ◽  
Author(s):  
Nicolas G. Brukman ◽  
Xiaohui Li ◽  
Benjamin Podbilewicz
Keyword(s):  
Cell Fusion ◽  
Generative Cell ◽  
Class Ii ◽  
Flowering Plants ◽  
Evolutionary Relationships ◽  
Gamete Fusion ◽  
Somatic Fusion ◽  
Viral Glycoproteins ◽  
Significant Divergence ◽  
Cell Cell

Gamete fusion is the climax of fertilization in all sexually reproductive organisms, from unicellular fungi to humans. Similarly to other cell-cell fusion events, gamete fusion is mediated by specialized proteins, named fusogens, that overcome the energetic barriers during this process. In recent years, HAPLESS 2/GENERATIVE CELL-SPECIFIC 1 (HAP2/GCS1) was identified as the fusogen mediating sperm-egg fusion in flowering plants and protists, being both essential and sufficient for the membrane merger in some species. The identification of HAP2/GCS1 in invertebrates, opens the possibility that a similar fusogen may be used in vertebrate fertilization. HAP2/GCS1 proteins share a similar structure with two distinct families of exoplasmic fusogens: the somatic Fusion Family (FF) proteins discovered in nematodes, and class II viral glycoproteins (e.g., rubella and dengue viruses). Altogether, these fusogens form the Fusexin superfamily. While some attributes are shared among fusexins, for example the overall structure and the possibility of assembly into trimers, some other characteristics seem to be specific, such as the presence or not of hydrophobic loops or helices at the distal tip of the protein. Intriguingly, HAP2/GCS1 or other fusexins have neither been identified in vertebrates nor in fungi, raising the question of whether these genes were lost during evolution and were replaced by other fusion machinery or a significant divergence makes their identification difficult. Here, we discuss the biology of HAP2/GCS1, its involvement in gamete fusion and the structural, mechanistic and evolutionary relationships with other fusexins.

scholarly journals Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens

2016 ◽  
Author(s):  
Clari Valansi ◽  
David Moi ◽  
Evgenia Leikina ◽  
Elena Matveev ◽  
Martín Graña ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Somatic Cell ◽  
Cell Fusion ◽  
Fusion Proteins ◽  
Mammalian Cells ◽  
Generative Cell ◽  
Target Cells ◽  
Complete Fusion ◽  
Gamete Fusion ◽  
Cell Cell

AbstractCell-cell fusion is inherent to any form of sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in different organisms but their exact role is unclear. Here we show that Arabidopsis HAP2/GCS1 expression in mammalian cells is sufficient to promote cell-cell fusion. Hemifusion and complete fusion depend on HAP2/GCS1 presence in both fusing cells. Furthermore, expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus and on the target cells results in HAP2-dependent virus-cell fusion. This bilateral requirement can be bypassed by replacing the plant gene with C. elegans EFF-1 somatic cell fusogen in one of the fusing cells or the virus, indicating that HAP2/GCS1 and EFF-1 share a similar fusion mechanism. Structural modeling of the HAP2/GCS1 protein family predicts that they are homologous to EFF-1 and class II fusion proteins from enveloped viruses (e.g. dengue and Zika viruses). We name this superfamily FUSEXINS: FUSion proteins essential for sexual reproduction and EXoplasmic merger of plasma membranes. Thus, Fusexins unify the origin and evolution of sexual reproduction, enveloped virus entry into cells and somatic cell fusion.

scholarly journals Arabidopsis HAP2/GCS1 is a gamete fusion protein homologous to somatic and viral fusogens

2017 ◽  
Vol 216 (3) ◽  
pp. 571-581 ◽  
Author(s):  
Clari Valansi ◽  
David Moi ◽  
Evgenia Leikina ◽  
Elena Matveev ◽  
Martín Graña ◽  
...  
Keyword(s):  
Sexual Reproduction ◽  
Somatic Cell ◽  
Cell Fusion ◽  
Fusion Proteins ◽  
Plasma Membranes ◽  
Generative Cell ◽  
Complete Fusion ◽  
Gamete Fusion ◽  
Origin And Evolution ◽  
Cell Cell

Cell–cell fusion is inherent to sexual reproduction. Loss of HAPLESS 2/GENERATIVE CELL SPECIFIC 1 (HAP2/GCS1) proteins results in gamete fusion failure in diverse organisms, but their exact role is unclear. In this study, we show that Arabidopsis thaliana HAP2/GCS1 is sufficient to promote mammalian cell–cell fusion. Hemifusion and complete fusion depend on HAP2/GCS1 presence in both fusing cells. Furthermore, expression of HAP2 on the surface of pseudotyped vesicular stomatitis virus results in homotypic virus–cell fusion. We demonstrate that the Caenorhabditis elegans Epithelial Fusion Failure 1 (EFF-1) somatic cell fusogen can replace HAP2/GCS1 in one of the fusing membranes, indicating that HAP2/GCS1 and EFF-1 share a similar fusion mechanism. Structural modeling of the HAP2/GCS1 protein family predicts that they are homologous to EFF-1 and viral class II fusion proteins (e.g., Zika virus). We name this superfamily Fusexins: fusion proteins essential for sexual reproduction and exoplasmic merger of plasma membranes. We suggest a common origin and evolution of sexual reproduction, enveloped virus entry into cells, and somatic cell fusion.

scholarly journals The late endosome-resident lipid bis(monoacylglycero)phosphate is a cofactor for Lassa virus fusion

2021 ◽  
Vol 17 (9) ◽  
pp. e1009488
Author(s):  
Ruben M. Markosyan ◽  
Mariana Marin ◽  
You Zhang ◽  
Fredric S. Cohen ◽  
Gregory B. Melikyan
Keyword(s):  
Cell Fusion ◽  
Host Cells ◽  
Target Cells ◽  
Lassa Virus ◽  
Viral Glycoprotein ◽  
Glycoprotein Complex ◽  
Late Endosomes ◽  
Viral Glycoproteins ◽  
Fusion Pores ◽  
Cell Cell

Arenavirus entry into host cells occurs through a low pH-dependent fusion with late endosomes that is mediated by the viral glycoprotein complex (GPC). The mechanisms of GPC-mediated membrane fusion and of virus targeting to late endosomes are not well understood. To gain insights into arenavirus fusion, we examined cell-cell fusion induced by the Old World Lassa virus (LASV) GPC complex. LASV GPC-mediated cell fusion is more efficient and occurs at higher pH with target cells expressing human LAMP1 compared to cells lacking this cognate receptor. However, human LAMP1 is not absolutely required for cell-cell fusion or LASV entry. We found that GPC-induced fusion progresses through the same lipid intermediates as fusion mediated by other viral glycoproteins–a lipid curvature-sensitive intermediate upstream of hemifusion and a hemifusion intermediate downstream of acid-dependent steps that can be arrested in the cold. Importantly, GPC-mediated fusion and LASV pseudovirus entry are specifically augmented by an anionic lipid, bis(monoacylglycero)phosphate (BMP), which is highly enriched in late endosomes. This lipid also specifically promotes cell fusion mediated by Junin virus GPC, an unrelated New World arenavirus. We show that BMP promotes late steps of LASV fusion downstream of hemifusion–the formation and enlargement of fusion pores. The BMP-dependence of post-hemifusion stages of arenavirus fusion suggests that these viruses evolved to use this lipid as a cofactor to selectively fuse with late endosomes.

scholarly journals Acquisition of Cell–Cell Fusion Activity by Amino Acid Substitutions in Spike Protein Determines the Infectivity of a Coronavirus in Cultured Cells

PLoS ONE ◽  
2009 ◽  
Vol 4 (7) ◽  
pp. e6130 ◽  
Author(s):  
Yoshiyuki Yamada ◽  
Xiao Bo Liu ◽  
Shou Guo Fang ◽  
Felicia P. L. Tay ◽  
Ding Xiang Liu
Keyword(s):  
Amino Acid ◽  
Cell Fusion ◽  
Cultured Cells ◽  
Spike Protein ◽  
Amino Acid Substitutions ◽  
Fusion Activity ◽  
Cell Cell

scholarly journals Elizabeth Chen: Fusing cells press closer

2014 ◽  
Vol 206 (5) ◽  
pp. 576-577
Author(s):  
Caitlin Sedwick
Keyword(s):  
Cell Fusion ◽  
Cell Cell

Chen studies cell–cell fusion in Drosophila myoblasts.

scholarly journals A Virus-Encoded Cell–Cell Fusion Machine Dependent on Surrogate Adhesins

2008 ◽  
Vol 4 (3) ◽  
pp. e1000016 ◽  
Author(s):  
Jayme Salsman ◽  
Deniz Top ◽  
Christopher Barry ◽  
Roy Duncan
Keyword(s):  
Cell Fusion ◽  
Cell Cell

Methodologies in the Study of Cell–Cell Fusion

Methods ◽  
1998 ◽  
Vol 16 (2) ◽  
pp. 215-226 ◽  
Author(s):  
Fredric S. Cohen ◽  
Grigory B. Melikyan
Keyword(s):  
Cell Fusion ◽  
Cell Cell

Cell‑cell fusion as an important mechanism of tumor metastasis (Review)

2021 ◽  
Vol 46 (1) ◽  
Author(s):  
Xiao-Chun Peng ◽  
Min Zhang ◽  
Ying-Ying Meng ◽  
Yan-Fang Liang ◽  
Ying-Ying Wang ◽  
...  
Keyword(s):  
Cell Fusion ◽  
Tumor Metastasis ◽  
Cell Cell

Herpes simplex virus glycoprotein B (gB) mutations define structural sites in domain I, the membrane proximal region, and the cytodomain that regulate entry.

2021 ◽  
Author(s):  
Qing Fan ◽  
Richard Longnecker ◽  
Sarah A. Connolly
Keyword(s):  
Cell Fusion ◽  
Virus Entry ◽  
Proximal Region ◽  
Glycoprotein B ◽  
Viral Fusion ◽  
Viral Fusion Protein ◽  
Membrane Proximal Region ◽  
Domain V ◽  
Domain I ◽  
Cell Cell

The viral fusion protein glycoprotein B (gB) is conserved in all herpesviruses and is essential for virus entry. During entry, gB fuses viral and host cell membranes by refolding from a prefusion to a postfusion form. We previously introduced three structure-based mutations (gB-I671A/H681A/F683A) into the domain V arm of the gB ectodomain that resulted in reduced cell-cell fusion. A virus carrying these three mutations (called gB3A) displayed a small plaque phenotype and remarkably delayed entry into cells. To identify mutations that could counteract this phenotype, we serially passaged the gB3A virus and selected for revertant viruses with increased plaque size. Genomic sequencing revealed that the revertant viruses had second-site mutations in gB, including E187A, M742T, and S383F/G645R/V705I/V880G. Using expression constructs encoding these mutations, only gB-V880G was shown to enhance cell-cell fusion. In contrast, all of the revertant viruses showed enhanced entry kinetics, underscoring the fact that cell-cell fusion and virus-cell fusion are different. The results indicate that mutations in three different regions of gB (domain I, the membrane proximal region, and the cytoplasmic tail domain) can counteract the slow entry phenotype of gB3A virus. Mapping these compensatory mutations to prefusion and postfusion structural models suggests sites of intramolecular functional interactions with the gB domain V arm that may contribute to the gB fusion function. Importance The nine human herpesviruses are ubiquitous and cause a range of disease in humans. Glycoprotein B (gB) is an essential viral fusion protein that is conserved in all herpesviruses. During host cell entry, gB mediates virus-cell membrane fusion by undergoing a conformational change. Structural models for the prefusion and postfusion form of gB exist, but the details of how the protein converts from one to the other are unclear. We previously introduced structure-based mutations into gB that inhibited virus entry and fusion. By passaging this entry-deficient virus over time, we selected second-site mutations that partially restore virus entry. The location of these mutations suggest regulatory sites that contribute to fusion and gB refolding during entry. gB is a target of neutralizing antibodies and defining how gB refolds during entry could provide a basis for the development of fusion inhibitors for future research or clinical use.

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