User:Cumberbatchbs/Cell–cell fusogens

( Exact Text Current Version 03-04-2020 )

Cell–cell fusogens are glycoproteins that facilitate the fusion of cells to cell membranes. Cell–cell fusion is critical for the merging of gamete genomes and the development of organs in multicellular organisms. Cell-cell fusion occurs when both actin cytoskeleton and fusogenic proteins properly rearrange across the cell membrane. This process is lead by actin-propelled membrane protrusions.

Identifiers

EFF-AFF are the identifiers for type 1 glycoproteins that makeup cell–cell fusogens. They were first identified when EFF1 mutants were found to "block cell fusion in all epidermal and vulval epithelia" in the roundworm, Caenorhabditis elegans. EFF-AFF is a family of type I membrane glycoproteins that act as cell–cell fusogens, named from 'Anchor cell fusion failure'. Because it was known that eff-1 mutants successfully fused the anchor cell and (uterine seam) utse syncytium to produce a continuous uterine-vulval tube, where these connections failed is where aff-1 mutants were discovered. Aff-1 was then deemed a necessity for this process in addition to the fusion of heterologous cells in C. elegans. The transmembrane forms of these proteins, like most viral fusogens, possess a N-terminal signal sequence followed by a long extracellular portion, a predicted transmembrane domain, and a short intracellular tail. " A striking conservation in the position and number of all 16 cysteines in the extracellular portion" of EFF-AFF proteins from different nematode species suggests that these proteins are folded in a similar 3D structure that is essential for their fusogenic activity. C. elegans AFF-1 and EFF-1 proteins are essential for developmental cell-to-cell fusion and can merge insect cells. "Thus FFs comprise an ancient family of cellular fusogens that can promote fusion when expressed on a viral particle."

( Draft of New Text 03-04-2020 )

How Cell-Cell Fusion Occurs

Before further discussing cell-cell fusogens, int must be understood what they are and how they occur. These are proteins that promote plasma membrane fusion between different cells. To be classified as a fusogen, the protein must be necessary for fusion, present on the fusing membrane when needed to be, and must be able to fuse unfamiliar membranes. These cells include but are not limited too: gametes, trophoblasts, epithelial, and other developmental cells. However, these fusogens do not only mediate cell-cell fusion, but can also perform neuron repairs, auto-fusion, and the sealing of phagosomes. Although these proteins may promote similar functions between cells, they all undergo individual mechanisms. These two mechanisms are known as unilateral (one fusing membrane needed to be present) and bilateral (same or different fusogens present at both membranes). For most fusogens mechanisms, the starting point is hemifusion. More specifically, the mechanism for cell-cell fusogens consist of four steps.

Steps of Cell-Cell Fusion

1. Cells must identify and be near each other.
2. Hemifusion occurs.
3. Fusion pore in hemifusion structure opens, thus allowing for cell contents to merge.
4. Cells completely join from pore expansion.

Applications

Roles in Gamete Fertilization

Cell-cell fusogens have several different applications. These chemical agents play a significant part in sexual and asexual reproduction. They promote the fusion of membrane bilayers. When looking at sexual reproduction, evidence has been found to prove that in mice, there are some mandatory sperm-egg fusogens responsible for fusion. Two particular proteins were IZUMO1 and CD9. After comparing the data of experiments done with plants, fungi, and invertebrates, it was seen that there may have been several crucial genes responsible for fertilization, however, like yeasts, there were no genes found to be sufficient enough for the fertilization process. As of late, another protein has been identified as a gamete fusogen, HAP2 or GCS1. Like the previous example, this too is found in plants, fungi, and invertebrates. This fusogen resembles that of the eukaryotic somatic fusogen mentioned earlier, EFF-1. The presence of HAP2 induces hemisufion and cell content mixing as well. Yet when considering asexual reproduction, somatic cells also can undergo cell-cell fusion or self-fusion. Two particular fusogens observed were SO and MAK-2. There is evidence supporting that these proteins control and regulate efficient protein concentration and localization.

Roles in Neuronal Repair

In the medical field, experiments have been done to test for the usefulness of these cell-cell fusogens in axonal nerve repairs and to determine its potential usefulness with other nerve cells. The current method for nerve repair Is to suture the cut ends of nerves. This is not efficient in its use because there is a lengthy recovery process along with a low functionality rate in the repaired nerves. When considering cell-cell fusogens as a potential answer, researchers were able to divide these fusogens into two groups based on their fusion mechanism, cell aggregation and membrane modification. A particular fusogen, PEG, was found to fit in both groups. It was this fusogen which was seen to be able to restore nerve cells in humans. Once operations were done within a certain time frame (12-hour period for human nerve repair and 24 hours for sciatic rat treatments), patient recovery was almost completely successful. Using this research, there is potential for repairing human nerve grafts in humans. Potential uses of cell-cell fusogens being studied are cancer vaccines and regenerating damaged cells. Additionally, any peripheral nerve in the body could be repaired, transferred tissues could work as soon as their sense return, and finally, any surgery done on nerves can be repaired as well resulting in an even quicker recovery.

References

This article incorporates text from the public domain Pfam and InterPro: IPR029213