MEMBRANE RECEPTORS: FUNCTIONS, TYPES, HOW THEY WORK - BIOLOGY - 2025

The membrane receptors are a class of cellular receptors that are located on the surface of the plasma membrane of cells, allowing detect chemicals by their nature can not cross the membrane.

Generally, membrane receptors are integral membrane proteins specialized in the detection of chemical signals such as peptide hormones, neurotransmitters and certain trophic factors; some drugs and toxins can also bind to these types of receptors.

Representative schematic of a membrane receptor. The ligands located on the outside of the membrane (1), the ligand-membrane receptor interaction (2) and (3) the subsequent signaling events are observed (Source: Wyatt Pyzynski via Wikimedia Commons)

They are classified according to the type of intracellular cascade to which they are coupled and which are those that determine the final effect on the corresponding cell, called the target cell or target cell.

Thus, three large groups have been described: those linked to ion channels, those linked to enzymes and those linked to protein G. The binding of ligands to receptors generates a conformational change in the receptor that triggers an intracellular signaling cascade in the target cell.

The signaling chains coupled to the membrane receptors make it possible to amplify the signals and generate transient or permanent responses or changes in the target cell. These intracellular signals are collectively called the "signal transduction system."

Features

The function of membrane receptors, and of other types of receptors in general, is to allow the communication of cells among themselves, in such a way that the different organs and systems of an organism work in a coordinated way to maintain homeostasis and respond to voluntary and automatic orders issued by the nervous system.

Thus, a chemical signal acting on the plasma membrane can trigger an amplified modification of various functions within the biochemical machinery of a cell and trigger a multiplicity of specific responses.

Through the signal amplification system, a single stimulus (ligand) is capable of generating immediate, indirect and long-term transient changes, modifying the expression of some genes within the target cell, for example.

Types

Cellular receptors are classified, according to their location, into: membrane receptors (those that are exposed in the cell membrane) and intracellular receptors (which can be cytoplasmic or nuclear).

Membrane receptors are of three types:

- Linked to ion channels

- Linked to enzymes

- Linked to G protein

Membrane receptors bound to ion channels

Also called ligand-gated ion channels, they are membrane proteins composed of 4 to 6 subunits that are assembled in such a way that they leave a central conduit or pore, through which ions pass from one side of the membrane to the other.

Example of the acetylcholine receptor, a receptor linked to an ion channel. The three conformational states of it are shown (Source: Laozhengzz via Wikimedia Commons)

These channels cross the membrane and have an extracellular end, where the binding site for the ligand is located, and another intracellular end that, in some channels, has a gate mechanism. Certain channels have an intracellular ligand site.

Enzyme-linked membrane receptors

These receptors are also transmembrane proteins. They have an extracellular end that presents the binding site for the ligand and that have associated with their intracellular end an enzyme that is activated by the binding of the ligand to the receptor.

Membrane receptors coupled or linked to G protein

G-protein-coupled receptors have an indirect mechanism for the regulation of the intracellular functions of target cells that involves transducer molecules called GTP-binding or binding proteins or G-proteins.

All these G protein-linked receptors are made up of a membrane protein that crosses the membrane seven times and are called metabotropic receptors. Hundreds of receptors linked to different G proteins have been identified.

How do they work?

In receptors bound to ion channels, the binding of the ligand to the receptor generates a conformational change in the structure of the receptor that can modify a gate, move the walls of the channel closer or further apart. With this they modify the passage of ions from one side of the membrane to the other.

Receptors bound to ion channels are, for the most part, specific for one type of ion, which is why receptors for K +, Cl-, Na +, Ca ++ channels, etc. have been described. There are also channels that allow two or more types of ions to pass through.

Most enzyme-linked receptors associate with protein kinases, especially the enzyme tyrosine kinase. These kinases are activated when the ligand binds to the receptor at its extracellular binding site. Kinases phosphorylate specific proteins in the target cell, modifying the cell's function.

Example of a membrane receptor linked to the enzyme tyrosine kinase (Source: Laozhengzz via Wikimedia Commons)

G protein-linked receptors activate cascades of biochemical reactions that end up modifying the function of various proteins in the target cell.

There are two types of G proteins which are heterotrimeric G proteins and monomeric G proteins. Both are inactively bound to GDP, but when the ligand is bound to the receptor, GDP is replaced by GTP and the G protein is activated.

In heterotrimeric G proteins, the α subunit bound to GTP dissociates from the ßγ complex, leaving the G protein activated. Both the α subunit bound to GTP and the free ßγ can mediate the response.

Schematic of a G protein coupled receptor (Source: Bensaccount at English Wikipedia via Wikimedia Commons)

Monomeric G proteins or small G proteins are also called Ras proteins because they have been described for the first time in a virus that produces sarcomatous tumors in rats.

When activated, they stimulate mechanisms mainly related to vesicular traffic and cytoskeletal functions (modification, remodeling, transport, etc.).

Examples

The acetylcholine receptor, linked to a sodium channel that opens upon binding to acetylcholine and which causes depolarization of the target cell, is a good example of membrane receptors linked to ion channels. In addition, there are three types of glutamate receptors that are ionotropic receptors.

Glutamate is one of the most important excitatory neurotransmitters in the nervous system. Its three types of ionotropic receptors are: NMDA (N-methyl-D-aspartate) receptors, AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionate) and kainate (acid kainic).

Their names are derived from the agonists that activate them and these three types of channels are examples of non-selective excitatory channels, since they allow the passage of sodium and potassium and in some cases small amounts of calcium.

Examples of enzyme-linked receptors are the insulin receptor, the TrK family of receptors or neurotrophin receptors, and the receptors for some growth factors.

The most important G protein-coupled receptors include muscarinic acetylcholine receptors, β-adrenergic receptors, olfactory system receptors, metabotropic glutamate receptors, receptors for many peptide hormones, and rhodopsin receptors of the retinal system.

References

1. Department of Biochemistry and Molecular Biophysics Thomas Jessell, Siegelbaum, S., & Hudspeth, AJ (2000). Principles of neural science (Vol. 4, pp. 1227-1246). ER Kandel, JH Schwartz, & TM Jessell (Eds.). New York: McGraw-hill.
2. Hulme, EC, Birdsall, NJM, & Buckley, NJ (1990). Muscarinic receptor subtypes. Annual review of pharmacology and toxicology, 30 (1), 633-673.
3. Cull-Candy, SG, & Leszkiewicz, DN (2004). Role of distinct NMDA receptor subtypes at central synapses. Sci. STKE, 2004 (255), re16-re16.
4. William, FG, & Ganong, MD (2005). Review of medical physiology. Printed in the United States of America, Seventeenth Edition, Pp-781.
5. Bear, MF, Connors, BW, & Paradiso, MA (Eds.). (2007). Neuroscience (Vol. 2). Lippincott Williams & Wilkins.