Signaling molecule

A signaling molecule is a molecule involved in transmitting information between cells of a living multicellular organism, or between organisms of the same or different species.

Cell signaling in multicellular organisms

In a multicellular organism, signaling between cells occurs either through release into the extracellular space, divided in paracrine signaling (over short distances) and endocrine signaling (over long distances), or by direct contact, known as juxtacrine signaling.[1] Autocrine signaling is a special case of paracrine signaling where the secreting cell has the ability to respond to the secreted signaling molecule.[2] Synaptic signaling is a special case of paracrine signaling (for chemical synapses) or juxtacrine signaling (for electrical synapses) between neurons and target cells. Signaling molecules interact with a target cell as a ligand to cell surface receptors, and/or by entering into the cell through its membrane or endocytosis for intracrine signaling. This generally results in the activation of second messengers, leading to various physiological effects.

A particular molecule is generally used in diverse modes of signaling, and therefore a classification by mode of signaling is not possible. At least three important classes of signaling molecules are widely recognized, although non-exhaustive and with imprecise boundaries, as such membership is non-exclusive and depends on the context:

Signaling molecules can belong to several chemical classes: lipids, phospholipids, amino acids, monoamines, proteins, glycoproteins, or gases. Signaling molecules binding surface receptors are generally large and hydrophilic (e.g. TRH, Vasopressin, Acetylcholine), while those entering the cell are generally small and hydrophobic (e.g. glucocorticoids, thyroid hormones, cholecalciferol, retinoic acid), but important exceptions to both are numerous, and a same molecule can act both via surface receptor or in an intracrine manner to different effects.[2] In intracrine signaling, once inside the cell, a signaling molecule can bind to intracellular receptors, other elements, or stimulate enzyme activity (e.g. gasses). The intracrine action of peptide hormones remains a subject of debate.[3]

Hydrogen sulfide is produced in small amounts by some cells of the human body and has a number of biological signaling functions. Only two other such gases are currently known to act as signaling molecules in the human body: nitric oxide and carbon monoxide.[4]

Intraspecies and interspecies signaling

Molecular signaling can occur between different organisms, whether unicellular or multicellular, the emitting organism produces the signaling molecule, secrete it into the environment, where it diffuses, and it is sensed or internalized by the receiving organism. In some cases of interspecies signaling, the emitting organism can actually be a host of the receiving organism, or vice-versa.

Intraspecies signaling occurs especially in bacteria, yeast, social insects, but also many vertebrates. The signaling molecules used by multicellular organisms are often called pheromones, they can have such purposes as alerting against danger, indicating food supply, or assisting in reproduction.[5] In unicellular organisms such as bacteria, signaling can be used to 'activate' peers from a dormant state, enhance virulence, defend against bacteriophages, etc.[6] In quorum sensing, which is also found in social insects, the multiplicity of individual signals has the potentiality to create a positive feedback loop, generating coordinated response, in this context the signaling molecules are called autoinducers.[7][8][9] This phenomenon is similar to the autocrine co-stimulation of multicellular organisms, on the other hand cellular differentiation occurs in bacteria, with altered response to peer signals, demonstrating a similarity with paracrine signaling of multicellular organisms.[10] This signaling mechanism may have been involved in evolution from unicellular to multicellular organisms.[7][11] Bacteria also use contact-dependent signaling, notably to limit their growth.[12][13]

Molecular signaling can also occur between individuals of different species, this has been particularly studied in bacteria.[14][15][16] Different bacterial species can coordinate to colonize a host and participate in common quorum sensing.[17] Therapeutic strategies to disrupt this phenomenon are being investigated.[18][19] Interactions mediated through signaling molecules are also thought to occur between the gut flora and their host, as part of their commensal or symbiotic relationship.[19][20]

References

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