Molecular cell signaling

Single celled organisms will sense their environment to seek food and may send out signals to other cells to behave symbiotically or reproduce. A classic example of this is the slime mold. The slime mold shows how intercellular communication with a small molecule e.g. cyclic AMP allows a simple organism to form from an organized aggregation of single cells.^[3] Research into cell signalling investigated a receptor specific to each signal or multiple receptors potentially being activated by a single signal.^[4] It is not only the presence or absence of a signal that is important but also the strength. Using a chemical gradient to coordinate cell growth and differentiation continues to be important as multicellular animals and plants become more complex. This type of intercellular communication within an organism is commonly referred to as cell signalling. This type of intercellular communication is typified by a small signalling molecule diffusing through the spaces around cells,^[5] often relying on a diffusion gradient forming part of the signalling response.

Cell junctions

Complex organisms may have molecules to hold the cells together which can also be involved in intercellular communication. Some binding molecules are termed the extracellular matrix and may involve longer molecules like cellulose for the cell wall in plants or collagen in animals. When the membranes of two cells are close they may form special types of cell junction which come in five broad types, adherens, desmosomes, gap, tight and tricellular junctions. Adherens, desmosomes, tight and tricellular junctions, serve structural roles. The structures they form also form parts of complex protein signaling pathways.^[6] In one respect tight junctions play a generic role in cell signaling in that they may form a tight zip around cells forming an barrier to stop even small unwanted signalling molecules getting between cells.^[7] Otherwise signalling molecules may spread to another group of cells which are not requiring the signal or allow signalling molecules escape to quickly from where they are needed.

Pannexins, connexins, innexins

Pannexins, connexins, and innexins are transmembrane proteins that are all named after the Latin term nexus, meaning to connect. They are grouped as they all share a similar structure of 4 transmembrane domains crossing the cell membrane in a similar way but they do not all share enough sequence homology to allow them to be considered directly related.^[2][8] Earlier investigations involving the connexins demonstrated cells forming a direct connection with each other using groups of connexins but not connections with the cell exterior. As such they were not considered to participate in the extracellular cell signalling at the time. Later studies made it apparent connexins could connect directly to the cell exterior meaning they are a conduit for the release an uptake of signalling molecules from the environment external to the cell.^[9] Furthermore, pannexins appear to do this to such an extent they may rarely if ever participate in direct cell to cell coupling.^[10] As indicated on the pannexin/innexin/connexin tree illustrated many animals do not appear to have pannexins/innexins/connexins, perhaps indicating there may be other similar proteins still to be discovered that serve to aid intercellular communication in these animals.^[2]

Septal pores

In fungi, pores crossing their cell walls that separate cellular compartments act as an ICC for the movement of molecules to their neighboring compartments.^[11]

Most red algae may have pores in the cell septum that partitions a cell/filament called a pit connection. As a leftover of the mitotic division it may be plugged up by the cell. There are also similar connections between neighboring cells/filaments that may allowing sharing of nutrients.^[12] Cells of a different species may initiate and form a pit connection with the host algae.^[13]

Plasmodesmata in plants

Plant cells usually have thick cell walls which need to be crossed if neighboring cells are to communicate directly. Plasmodesmata form a pipe through the cell wall forming an ICC. The pipe has another smaller membranous pipe concentric to it connecting the endoplasmic reticulum of the two cells via a tube called the desmotubule. The larger pipe also contains cytoskeletal and other elements. It is presumed viruses use plasmodesmata as a route through the cell walls to spread through the plant.^[14]

Gap junctions in animals

Gap junctions can form intercellular links, effectively a tiny direct regulated "pipe" called a connexon pair between the cytoplasms of the two cells that form the junction. 6 connexins make a connexon, 2 connexons make a connexon pair so 12 connexin proteins build each tiny ICC. This ICC allows two cells to communicate directly while being sealed from the outside world.^[15] Cells may form one or thousands of these tiny ICCs between them and their other neighbors, potentially forming large networks of directly linked cells. The connexon pairs form ICCs that can transport water, many other molecules up to around 1000 atoms in size^[16] and can be very rapidly signaled to turn on and off as required. These ICCs are also communicating electrical signals that can be rapidly turned on and off. To add to their versatility there are a range of these ICC types due to their being over 20 different connexins with different properties that can combine with each other in a variety of ways. The variety of potential signaling combinations that results is enormous. A much studied example of gap junctions electrical signalling abilities is in the electrical synapses found on nerves.^[17][18][19] In heart muscle gap junctions function to coordinate the beating of the heart. Adding even further to their versatility gap junctions can also function to form a direct connection to the exterior of a cell paralleling the functioning of the protein cousin the pannexins which are explained elsewhere.

Intercellular bridge

Intercellular bridges are larger than gap junction ICCs so are able to allow the movement of not only small signaling molecules but also large DNA molecules or even whole cell organelles. They are maintained between two cells allowing them to exchange cytoplasmic contents and are frequently observed when cells need intimate communication such as when they are reproducing. They are found in Prokaryotes for exchanging DNA, small organisms such as Pinnularia, Valonia ventricosa, Volvox, C. elegans^[20] and mitosis generally (Cytokinesis),^[21] Blepharisma for sexual reproduction and during Meiosis including Spermatocytogenesis to synchronise development of germ cells and oogenesis in larger organisms. Bridges have shown to assist in cell migration as shown in the adjacent picture.^[22] Cytoplasmic bridges can also be used to attack another cell as in the case of Vampirococcus.

Cell fusion

Cells that require a more permanent, extensive cytoplasmic linkage may fuse with each other to varying degrees in many cases forming one large cell or syncytium. This happens extensively during the development of skeletal muscle forming large muscle fibers. Later it was confirmed in other tissues such as the eye lens. Though both involving cell fibers, in the case of the eye lens the cell fusion is more limited in scope resulting in a less extensively fused stratified syncytium.^[23]

Ephaptic coupling

When groups of nerve cells form another type of intercellular communication called ephaptic coupling can arise. It was first quantified by Katz in 1940^[40] but it has been difficult to associate any one structure or "ephapse" with this form of communication. There are reductionist attempts to associate particular groups of nerve cells exhibiting ephaptic coupling with particular functions in the brain.^[41] As yet there are no studies on the simplest neural systems such as the polar bodies of Ctenophores to see if ephaptic coupling may explain some of their more complex behaviors.^[39]