4.4. Cell communication

In the same way that social organisations require communication between individuals and their environment to maintain societal cohesion, cells must also be able to interact with their environment.

In order to respond to external stimuli, cells have developed complex communication systems that allow them to receive messages, transfer information across the plasma membrane and produce changes within the cell in response to those messages.

Cells of multicellular organisms constantly send and receive messages to coordinate the actions of cells, tissues and distant organs. The capacity to send messages in an effective and quick way allows cells to coordinate and adjust their functions.
This capacity to communicate via chemical signals, initially developed by individual cells, was a vital attribute for the evolution of multicellular organisms.

Signalling molecules and cellular receptors

Cells are in contact via intercellular signaling (communication between cells) and intracellular signaling (communication within the cell).
Signalling cells are responsible for secreting ligands[1] or they bind to target cells, triggering a event chain within them.

In multicellular organisms, chemical signalling is classified into four categories: endocrine signalling, autocrine signalling, paracrine signalling and direct signalling by gap junctions (juxtacrine signalling).
Endocrine signalling is performed by hormones across long distances through the bloodstream.
In autocrine signalling, signals are received by the same cell that sends them or other close cells of the same type.
Paracrine signalling also acts at short distances under the action of ligands that travel through the liquid medium of the extracellular matrix.
Lastly, gap junctions enable signalling molecules to flow between neighbouring cells.
Types of cell signalling

Types of receptors

Receptors are proteins located within, or on the surface of target cells that bind to ligands. Receptors are thus divided into two different classes: internal receptors and cell-surface receptors.

Internal receptors are located in the cell cytoplasm attached to the ligand molecules that pass through the cell membrane. These receptor-ligand complexes move to the nucleus and there they interact directly with the cellular DNA.

Cell-surface receptors convey a signal from outside the cell to the cytoplasm. They comprise three components: a region outside the cell to which the ligand binds (also called extracellular domain), a hydrophobic central region in the membrane and the intracellular domain within the cell.
They are divided into three categories:
      Ion channel-linked receptors[2]. When they bind to their specific ligands they form a channel across the plasma membrane through which certain ions can pass.
      G-protein-linked receptors. They interact with G-proteins[3] on the cytoplasmatic side of the cell membrane.
Once the G-protein binds to the receptor, the resultant compound activates the G-protein, which releases GDP[4] and pick up GTP[5], interacting with other enzymes or ionic channels to transmit the signal.
      Enzyme-linked receptors. They carry a signal of membrane-bound enzymes from outside the cell to the intracellular domain. The union with the ligand causes the enzyme activation.
Types of cell receptors
Small hydrophobic ligands (e.g. steroids) are able to penetrate the cell membrane and stick to internal receptors.
On the other hand, hydrophilic receptors (soluble in water) are unable to pass through the membrane; consequently they link with cell-surface receptors, which convey signals inside the cell.

Propagation of the signal

The binding of a ligand to a receptor enables signal transduction[6] throughout the cell.
The chain of events that creates signal transmission is called the ‘signalling cascade’ or ‘signalling pathway’. This pathway can be very complex as a consequence of the interaction among different proteins.
One of the most important events in this process is the phosphorylation of molecules by way of specific enzymes known as kinases[7].
Protein phosphorylation processPhosphorylation adds a phosphate group to residues (R-groups) of the following amino acids: serine, threonine and tyrosine, activating and deactivating the protein to these amino acids belong to or changing its shape. Also, small molecules such as nucleotides can be phosphorylated.

Once a receptor has been activated, the signal propagates throughout the cell via the cytoplasm by modifying the behaviour of certain cellular proteins. These signals are released by small non-protein molecules, called second messengers. Among them are: cyclic AMP (cAMP), calcium ions (Ca2+), inositol triphosphate (IP3) and diacylglycerol.

Response to the signal

The initiation of signalling routes is triggered in response to external stimuli. The effects of these responses are quite diverse, depending on the type of cell involved, as well as internal and external conditions.
Among these effects are cell growth, protein synthesis, changes in the cell metabolism and even cell death.

But these signalling routes have their most significant impact on the cell by initiating gene expression[8].
Thus, some routes activate enzymes that interact with transcription factors of RNA and others regulate protein transduction from mRNA.
Other routes again, however, work on the cellular metabolism, e.g. they enable muscle cells to communicate their functional energy requirements (these requirements are in the form of glucose).

Signalling routes play a very significant role in cellular growth too, which is stimulated by external signals, called ‘growth factors’ (types of ligands that bind to cell-surface receptors).
Uncontrolled cell growth lead to cancer. Cancer’s origin is often due to mutations presented by those genes responsible for encoding the proteins that are part of signalling pathways.

When a cell is damaged, is unnecessary or is potentially dangerous, the organism must initiate the process that triggers programmed cell death or apoptosis. Apoptosis allows a cell to die in a controlled way, avoiding the release of potentially harmful molecules, in contrast to uncontrolled death or necrosis.
Necrosis and apoptosis processes
Cell signalling controls the process of apoptosis so that the dismantling of cells is carried out in an organised way, as well as the efficiently recycling the different components of dead cells.

The end of the signalling cascade is very important in ensuring that the signal response is appropriate both in time and intensity.
Two of the most common ways of ending signalling within cells is with the degradation of signalling molecules and dephosphorylation of intermediate products of the pathway (previously phosphorylated) via phosphatase[9] enzyme.

Some of the abnormal signals originated in tumour cells are good evidence that termination of cellular cascades at the appropriate time is as important as the timing of initiation.

[1] Small volatile or soluble molecules that bind to other specific molecules (receptors) releasing a signal in the process.
[2] Cell-surface receptors in the channels of plasma membranes that open when a ligand sticks to its extracellular domain.
[3] Signal transducers that transmit information from the receptor to effector proteins.
[4] Guanosine diphosphate: dephosphorylation product of GTP.
[5] Guanosine triphosphate is a purine nucleoside triphosphate used in the cell metabolism. 
[6] Transmission of a signal from outside the cell to its inside.
[7] Enzymes that catalyse the transfer of a phosphate group from ATP to another molecule.
[8] Process by which cells transform the encoding information of amino acids into necessary proteins for their development and functioning.
[9] Enzyme in charge of removing the phosphate group of a molecule that has been phosphorylated.

Sources: OpenStax College, Biology. OpenStax College. 30 May 2013.

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