Cell-cell fusion remains the least understood type of membrane fusion process. However, the last few years have brought about major advances in understanding fusion between gametes, myoblasts, macrophages, trophoblasts, epithelial, cancer, and other cells in normal development and in diseases. While different cell fusion processes appear to proceed via similar membrane rearrangements, proteins that have been identified as necessary and sufficient for cell fusion (fusogens) use diverse mechanisms. Some fusions are controlled by a single fusogen; other fusions depend on several proteins that either work together throughout the fusion pathway or drive distinct stages. Furthermore, some fusions require fusogens to be present on both fusing membranes, and in other fusions, fusogens have to be on only one of the membranes. Remarkably, some of the proteins that fuse cells also sculpt single cells, repair neurons, promote scission of endocytic vesicles, and seal phagosomes. In this review, we discuss the properties and diversity of the known proteins mediating cell-cell fusion and highlight their different working mechanisms in various contexts.
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The C. elegans developmental fusogen EFF-1 mediates homotypic fusion in heterologous cells and in vivo
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Lipocalin signaling controls unicellular tube development in the Caenorhabditis elegans excretory system
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The Caenorhabditis elegans GATA factor ELT-1 works through the cell proliferation regulator BRO-1 and the Fusogen EFF-1 to maintain the seam stem-like fate
A pair of co-opted retroviral envelope syncytin genes is required for formation of the two-layered murine placental syncytiotrophoblast
Actin-propelled invasive membrane protrusions promote fusogenic protein engagement during cell-cell fusion
A transgenic insertion on mouse chromosome 17 inactivates a novel immunoglobulin superfamily gene potentially involved in sperm-egg fusion
Efficient reovirus- and measles virus-mediated pore expansion during syncytium formation is dependent on annexin A1 and intracellular calcium
A compact, multifunctional fusion module directs cholesterol-dependent homomultimerization and syncytiogenic efficiency of reovirus p10 FAST proteins
Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization
The Atlastin C-terminal tail is an amphipathic helix that perturbs the bilayer structure during endoplasmic reticulum homotypic fusion
The cytoplasmic domain of the gamete membrane fusion protein HAP2 targets the protein to the fusion site in Chlamydomonas and regulates the fusion reaction
Osteoclast fusion is initiated by a small subset of RANKL-stimulated monocyte progenitors, which can fuse to RANKL-unstimulated progenitors
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The EFF-1A Cytoplasmic Domain Influences Hypodermal Cell Fusions in C. elegans But Is Not Dependent on 14-3-3 Proteins
Novel function of stabilin-2 in myoblast fusion: the recognition of extracellular phosphatidylserine as a "fuse-me" signal
Two HAP2-GCS1 homologs responsible for gamete interactions in the cellular slime mold with multiple mating types: Implication for common mechanisms of sexual reproduction shared by plants and protozoa and for male-female differentiation
Structure-Function Studies Link Class II Viral Fusogens with the Ancestral Gamete Fusion Protein HAP2
Extrinsic Repair of Injured Dendrites as a Paradigm for Regeneration by Fusion in Caenorhabditis elegans
Spectraplakin Induces Positive Feedback between Fusogens and the Actin Cytoskeleton to Promote Cell-Cell Fusion
WASP-Arp2/3-dependent actin polymerization influences fusogen localization during cell-cell fusion in Caenorhabditiselegans embryos
Dynein and EFF-1 control dendrite morphology by regulating the localization pattern of SAX-7 in epidermal cells
let-7 miRNA controls CED-7 homotypic adhesion and EFF-1-mediated axonal self-fusion to restore touch sensation following injury
Phosphatidylserine save-me signals drive functional recovery of severed axons in Caenorhabditis elegans
Mutational analysis of IZUMO1R in women with fertilization failure and polyspermy after in vitro fertilization
Cardiomyocyte differentiation of mesenchymal stem cells from bone marrow: new regulators and its implications
OC-STAMP promotes osteoclast fusion for pathogenic bone resorption in periodontitis via up-regulation of permissive fusogen CD9
Spectrin is a mechanoresponsive protein shaping fusogenic synapse architecture during myoblast fusion
Evolutionary diversification of the HAP2 membrane insertion motifs to drive gamete fusion across eukaryotes
Dedifferentiation, transdifferentiation and cell fusion: in vivo reprogramming strategies for regenerative medicine
Myomaker and Myomerger Work Independently to Control Distinct Steps of Membrane Remodeling during Myoblast Fusion
Cell fusion potentiates tumor heterogeneity and reveals circulating hybrid cells that correlate with stage and survival
Spatiotemporal regulation of the GPCR activity of BAI3 by C1qL4 and Stabilin-2 controls myoblast fusion
Serial block-face scanning electron microscopy reveals neuronal-epithelial cell fusion in the mouse cornea
Myocyte-derived Myomaker expression is required for regenerative fusion but exacerbates membrane instability in dystrophic myofibers
RNA-Seq identifies genes whose proteins are upregulated during syncytia development in murine C2C12 myoblasts and human BeWo trophoblasts
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