Asyncytium (/sɪnˈsɪʃiəm/;pl.:syncytia; fromGreek: σύνsyn "together" and κύτοςkytos "box, i.e. cell") orsymplasm is amultinucleatecell that can result from multiple cell fusions of uninuclear cells (i.e., cells with a singlenucleus), in contrast to acoenocyte, which can result from multiple nuclear divisions without accompanyingcytokinesis.[1] The muscle cell that makes up animalskeletal muscle is a classic example of a syncytium cell. The term may also refer to cells interconnected by specialized membranes withgap junctions, as seen in theheart muscle cells and certain smooth muscle cells, which are synchronized electrically in anaction potential.
The field ofembryogenesis uses the wordsyncytium to refer to the coenocyticblastoderm embryos ofinvertebrates, such asDrosophila melanogaster.[2]
Inprotists, syncytia can be found in somerhizarians (e.g.,chlorarachniophytes,plasmodiophorids,haplosporidians) andacellular slime moulds,dictyostelids (amoebozoans),acrasids (Excavata) andHaplozoon.
Some examples ofplant syncytia, which result duringplant development, include:
A syncytium is the normal cell structure for manyfungi.[6]
Most fungi ofBasidiomycota exist as adikaryon in which thread-like cells of themycelium are partially partitioned into segments each containing two differing nuclei, called aheterokaryon.
The neurons which makes up the subepithelialnerve net in comb jellies (Ctenophora) are fused into a neural syncytium, consisting of a continuous plasma membrane instead of being connected throughsynapses.[7]
A classic example of a syncytium is the formation ofskeletal muscle. Largeskeletal muscle fibers form by the fusion of thousands of individual muscle cells. Themultinucleated arrangement is important in pathologic states such asmyopathy, where focal necrosis (death) of a portion of a skeletal muscle fiber does not result in necrosis of the adjacent sections of that same skeletal muscle fiber, because those adjacent sections have their own nuclear material. Thus, myopathy is usually associated with such "segmental necrosis", with some of the surviving segments being functionally cut off from their nerve supply via loss of continuity with theneuromuscular junction.
The syncytium ofcardiac muscle is important because it allows rapid coordinated contraction of muscles along their entire length.Cardiac action potentials propagate along the surface of the muscle fiber from the point ofsynaptic contact throughintercalated discs. Although a syncytium, cardiac muscle differs because the cells are not long and multinucleated. Cardiac tissue is therefore described as a functional syncytium, as opposed to the true syncytium of skeletal muscle.
Smooth muscle in thegastrointestinal tract is activated by a composite of three types of cells –smooth muscle cells (SMCs),interstitial cells of Cajal (ICCs), andplatelet-derived growth factor receptor alpha (PDGFRα) that are electrically coupled and work together as an SIP functional syncytium.[8][9]
Certain animal immune-derived cells may form aggregate cells, such as theosteoclast cells responsible forbone resorption.
Another important vertebrate syncytium is in theplacenta of placental mammals. Embryo-derived cells that form the interface with the maternal blood stream fuse together to form a multinucleated barrier – thesyncytiotrophoblast. This is probably important to limit the exchange of migratory cells between the developing embryo and the body of the mother, as someblood cells are specialized to be able to insert themselves between adjacentepithelial cells. The syncytial epithelium of the placenta does not provide such an access path from the maternal circulation into the embryo.
Much of the body ofHexactinellid sponges is composed of syncitial tissue. This allows them to form their largesiliceousspicules exclusively inside their cells.[10]
The fine structure of thetegument inhelminths is essentially the same in both thecestodes andtrematodes. A typical tegument is 7–16 μm thick, with distinct layers. It is a syncytium consisting of multinucleated tissues with no distinctcell boundaries. The outer zone of the syncytium, called the "distal cytoplasm," is lined with aplasma membrane. This plasma membrane is in turn associated with a layer of carbohydrate-containingmacromolecules known as theglycocalyx, that varies in thickness from onespecies to another. The distalcytoplasm is connected to the inner layer called the "proximal cytoplasm", which is the "cellular region or cyton or perikarya" through cytoplasmic tubes that are composed ofmicrotubules. The proximal cytoplasm containsnuclei,endoplasmic reticulum,Golgi complex,mitochondria,ribosomes,glycogen deposits, and numerousvesicles.[11] The innermost layer is bounded by a layer ofconnective tissue known as the "basal lamina". The basal lamina is followed by a thick layer ofmuscle.[12]
Syncytia can also form when cells are infected with certain types ofviruses, notablyHSV-1,HIV,MeV,SARS-CoV-2, andpneumoviruses, e.g.respiratory syncytial virus (RSV). These syncytial formations create distinctivecytopathic effects when seen inpermissive cells. Because many cells fuse together, syncytia are also known as multinucleated cells,giant cells, or polykaryocytes.[13] During infection, viral fusion proteins used by the virus toenter the cell are transported to the cell surface, where they can cause the hostcell membrane tofuse with neighboring cells.
Typically, the viral families that can cause syncytia are enveloped, because viral envelope proteins on the surface of the host cell are needed to fuse with other cells.[14] Certain members of theReoviridae family are notable exceptions due to a unique set of proteins known as fusion-associated small transmembrane (FAST) proteins.[15] Reovirus induced syncytium formation is not found in humans, but is found in a number of other species and is caused by fusogenicorthoreoviruses. These fusogenic orthoreoviruses include reptilian orthoreovirus, avian orthoreovirus, Nelson Bay orthoreovirus, and baboon orthoreovirus.[16]
HIV infects Helper CD4+T cells and makes them produce viral proteins, including fusion proteins. Then, the cells begin to display surface HIVglycoproteins, which areantigenic. Normally, acytotoxic T cell will immediately come to "inject"lymphotoxins, such asperforin orgranzyme, that will kill the infected T helper cell. However, if T helper cells are nearby, thegp41 HIV receptors displayed on the surface of the T helper cell will bind to other similar lymphocytes.[17] This makes dozens of T helper cells fuse cell membranes into a giant, nonfunctional syncytium, which allows the HIV virion to kill many T helper cells by infecting only one. It is associated with a faster progression of the disease[18]
Themumps virus usesHN protein to stick to a potential host cell, then, thefusion protein allows it to bind with the host cell. TheHN andfusion proteins are then left on the host cell walls, causing it to bind with neighbourepithelial cells.[19]
Mutations withinSARS-CoV-2 variants containspike protein variants that can enhance syncytia formation.[20] TheproteaseTMPRSS2 is essential for syncytia formation.[21] Syncytia can allow the virus to spread directly to other cells, shielded from neutralizing antibodies and other immune system components.[20] Syncytia formation in cells can be pathological to tissues.[20]
"Severe cases ofCOVID-19 are associated with extensive lung damage and the presence of infected multinucleated syncytialpneumocytes. The viral and cellular mechanisms regulating the formation of these syncytia are not well understood,"[22] but membrane cholesterol seems necessary.[23][24]
The syncytia appear to be long-lasting; the "complete regeneration" of the lungs after severeflu "does not happen" with COVID-19.[25]
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