Human Complexity
We humans are a mechanism worth studying. We are made up of trillions of individual components, cells, that constantly communicate with one another to form what we are. There are hundreds of cell types (cells specialized in particular functions): muscle cells, neurons, cells of the immune system, etc.
In spite of this overwhelming diversity, all of them contain the same genetic information: our genome.
Among vast amounts of different information, the genome contains the recipes to build tens or hundreds of thousands of proteins (what we know as genes).
The presence or absence of certain proteins, their concentration and the interaction between them and the genome itself determine the shape and the behavior of a cell. Therefore, cell types are ultimately distinguished by the proteins they present. In other words, their identity is determined by the proteins or genes they express (gene expression is the process by which information from a gene is used in the synthesis of a functional gene product, such as a protein).
In this manner, cells that have different shapes and functions are generated from the same genome: muscle cells, cells of the immune system, respiratory epithellium cells, etc.
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Integrating the Environment: Proteins
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The great majority of events that take place within the cell result from the action of proteins. Among many other functions, proteins determine cell response to changes in their environment or signals sent by other cells. In a way, cells have to understand what the environment or other cells are communicating to them and act accordingly.
Environmental signals are identified by “sensor” proteins (which we can also call “receptors” of an external signal). We can draw analogies from the receptors around us: radio antennas, fiber optic inputs, thermometers, barometers, seismographs, microphones, keyboards, cameras, etc.
When cell receptors identify a change, they emit a signal that usually travels to the interior of the cell. Sometimes, this trajectory is determined by the interaction of different proteins in what is known as the signaling pathway. Within the cell, this signaling pathway will produce a response (which implies changes in the behavior or expression of other proteins).
The response to external stimuli is essential for a mechanism of trillions of cells such as ours to function properly.
The Family of Nuclear Receptors
There is a particularly relevant family of proteins that play the role of receptors and effectors on their own. They receive the signal and act accordingly.
We are talking about the family of nuclear receptors, a fascinating group of proteins of an enormous physiological and pharmacological relevance (over 10% of currently available drugs act on members of this family).
These proteins are grouped in the same family due to their close evolutionary relationship; they share a common basic structure. 48 nuclear receptors have been identified in humans.
If Receptors Are the Answer, What Is the Question?
In general terms, how cells respond to external changes or signals is determined by the presence of the cell membrane, the barrier that separates cells from the surrounding environment.
In this scenario, extracellular signals require a membrane protein capable of identifying them, as well as different proteins that transport this signal from the membrane to the interior of the cell. We can think of it as a relay system that carries an urgent message from the border of a country to its capital.
However, nuclear receptors are always located within the cell. Then, how do they recognize the external signal?
Nuclear receptors recognize signals that, due to their chemical structure, are capable of passing through the cell membrane .
Going back to the historical simile, nuclear receptors would receive messages directly from carrier pigeons, which can cross borders with ease.
Signals: Ligands
Molecules that are recognized by receptor proteins are called ligands. When they recognize ligands that can enter the cell, nuclear receptors receive the signal and can act accordingly.
They are both receptors and effectors. All in one.
Ligands of nuclear receptors share their ability to go through the lipid bilayer, although they are a different set of molecules. Among these ligands we find thyroid hormones (estrogens, androgens, glucocorticoids, vitamin D), retinoic acids, fatty acids, leukotrienes, prostaglandins, etc.
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Images: Adam Nieman, reynermedia, Medialab Katowice, John Carrel, ufopilot, Dartmouth College
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Taking Apart a Receptor [icon style=”default” size=”20″]fa-chevron-right[/icon]
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