A syncytium (; : syncytia; from Ancient Greek: σύν syn "together" and κύτος kytos "box, i.e. cell") (also synctitium) or symplasm is a multinucleate cell that can result from multiple cell fusions of uninuclear cells (i.e., cells with a single Cell nucleus), in contrast to a coenocyte, which can result from multiple nuclear divisions without accompanying cytokinesis.
The field of embryogenesis uses the word syncytium to refer to the coenocytic blastoderm embryos of , such as Drosophila melanogaster.[Willmer, P. G. (1990). Invertebrate Relationships: Patterns in Animal Evolution. Cambridge University Press, Cambridge.]
Physiological examples
Protists
In
, syncytia can be found in some
(e.g., chlorarachniophytes,
,
) and
slime moulds,
(
),
(
Excavata) and
Haplozoon.
Plants
Some examples of
plant syncytia, which result during plant development, include:
Fungi
A syncytium is the normal cell structure for many
fungus.
[|]
Most fungi of Basidiomycota exist as a dikaryon in which thread-like cells of the mycelium are partially partitioned into segments each containing two differing nuclei, called a heterokaryon.
Animals
Nerve net
The neurons which makes up the subepithelial
nerve net in comb jellies (
Ctenophora) are fused into a neural syncytium, consisting of a continuous plasma membrane instead of being connected through
.
Skeletal muscle
A classic example of a syncytium is the formation of
skeletal muscle. Large
skeletal muscle fibers form by the fusion of thousands of individual muscle cells. The
multinucleated arrangement is important in pathologic states such as
myopathy, 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 the neuromuscular junction.
Cardiac muscle
The syncytium of
cardiac 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 of
synapse contact through intercalated 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
Smooth muscle in the gastrointestinal tract is activated by a composite of three types of cells – smooth muscle cells (SMCs), interstitial cells of Cajal (ICCs), and platelet-derived growth factor receptor alpha (PDGFRα) that are electrically coupled and work together as an SIP functional syncytium.
Osteoclasts
Certain animal immune-derived cells may form aggregate cells, such as the
osteoclast cells responsible for
bone resorption.
Placenta
Another important vertebrate syncytium is in the
placenta of placental mammals. Embryo-derived cells that form the interface with the maternal blood stream fuse together to form a multinucleated barrier – the syncytiotrophoblast. This is probably important to limit the exchange of migratory cells between the developing embryo and the body of the mother, as some blood cells are specialized to be able to insert themselves between adjacent
epithelium cells. The syncytial epithelium of the placenta does not provide such an access path from the maternal circulation into the embryo.
Glass sponges
Much of the body of
Hexactinellid sponges is composed of syncitial tissue. This allows them to form their large
Siliceous sponge Sponge spicule exclusively inside their cells.
Tegument
The fine structure of the tegument in
is essentially the same in both the
cestodes and
trematodes. A typical tegument is 7–16 μm thick, with distinct layers. It is a syncytium consisting of multinucleated tissues with no distinct cell boundaries. The outer zone of the syncytium, called the "distal cytoplasm," is lined with a
plasma membrane. This plasma membrane is in turn associated with a layer of carbohydrate-containing
known as the
glycocalyx, that varies in thickness from one
species to another. The distal
cytoplasm 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 of
. The proximal cytoplasm contains
Cell nucleus, endoplasmic reticulum,
Golgi complex,
mitochondria,
ribosomes,
Glycogen, and numerous vesicles.
The innermost layer is bounded by a layer of connective tissue known as the "
basal lamina". The basal lamina is followed by a thick layer of
muscle.
Pathological examples
Viral infection
Syncytia can also form when cells are infected with certain types of
, notably
Herpes simplex,
HIV,
Measles virus, SARS-CoV-2, and
Pneumoviridae, e.g. respiratory syncytial virus (RSV). These syncytial formations create distinctive cytopathic effects when seen in
. Because many cells fuse together, syncytia are also known as multinucleated cells,
, or polykaryocytes.
During infection, viral fusion proteins used by the virus to
viral entry the cell are transported to the cell surface, where they can cause the host
cell membrane to fuse with neighboring cells.
Reoviridae
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.
Certain members of the
Reoviridae family are notable exceptions due to a unique set of proteins known as fusion-associated small transmembrane (FAST) proteins.
Reovirus induced syncytium formation is not found in humans, but is found in a number of other species and is caused by fusogenic
. These fusogenic orthoreoviruses include reptilian orthoreovirus, avian orthoreovirus, Nelson Bay orthoreovirus, and baboon orthoreovirus.
HIV
HIV infects Helper CD4
+ and makes them produce viral proteins, including fusion proteins. Then, the cells begin to display surface HIV
, which are
. Normally, a cytotoxic T cell will immediately come to "inject"
, such as
perforin or
granzyme, that will kill the infected T helper cell. However, if T helper cells are nearby, the gp41 HIV receptors displayed on the surface of the T helper cell will bind to other similar lymphocytes.
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
Mumps
The
mumps virus uses HN protein to stick to a potential host cell, then, the fusion protein allows it to bind with the host cell. The HN and fusion proteins are then left on the host cell walls, causing it to bind with neighbour
Epithelium cells.
COVID-19
Mutations within SARS-CoV-2 variants contain
spike protein variants that can enhance syncytia formation.
The
protease TMPRSS2 is essential for syncytia formation.
Syncytia can allow the virus to spread directly to other cells, shielded from neutralizing antibodies and other immune system components.
Syncytia formation in cells can be pathological to tissues.
"Severe cases of COVID-19 are associated with extensive lung damage and the presence of infected multinucleated syncytial . The viral and cellular mechanisms regulating the formation of these syncytia are not well understood,"[ As of 13 October 2020: accepted for publication and undergone full peer review but not copyedited, typeset, paginated, or proofread.] but membrane cholesterol seems necessary.
The syncytia appear to be long-lasting; the "complete regeneration" of the lungs after severe flu "does not happen" with COVID-19.
See also
