Types of Receptors

A cell within a multicellular organism may need to signal to other cells that are at various distances from the original cell (Figure 1). Not all cells are affected by the same signals. Different types of signaling are used for different purposes.

The illustration shows four forms of chemical signaling. In autocrine signaling, a cell targets itself. In signaling across a gap junction, a cell targets a cell connected via gap junctions. In paracrine signaling, a cell targets a nearby cell. In endocrine signaling, a cell targets a distant cell via the bloodstream
Figure 1 In chemical signaling, a cell may target itself (autocrine signaling), a cell connected by gap junctions, a nearby cell (paracrine signaling), or a distant cell (endocrine signaling). Paracrine signaling acts on nearby cells, endocrine signaling uses the circulatory system to transport ligands, and autocrine signaling acts on the signaling cell. Signaling via gap junctions involves signaling molecules moving directly between adjacent cells.
Receptors are protein molecules inside the target cell or on its surface that receive a chemical signal. Chemical signals are released by signaling cells in the form of small, usually volatile or soluble molecules called ligands. A ligand is a molecule that binds another specific molecule, in some cases, delivering a signal in the process. Ligands can thus be thought of as signaling molecules. Ligands and receptors exist in several varieties; however, a specific ligand will have a specific receptor that typically binds only that ligand.

Internal receptors

Internal receptors, also known as intracellular or cytoplasmic receptors, are found in the cytoplasm of the cell and respond to hydrophobic ligand molecules that are able to travel across the plasma membrane. Once inside the cell, many of these molecules bind to proteins that act as regulators of mRNA synthesis. Recall that mRNA carries genetic information from the DNA in a cell’s nucleus out to the ribosome, where the protein is assembled. When the ligand binds to the internal receptor, a change in shape is triggered that exposes a DNA-binding site on the receptor protein. The ligand-receptor complex moves into the nucleus, then binds to specific regions of the DNA and promotes the production of mRNA from specific genes (Figure 2). Internal receptors can directly influence gene expression (how much of a specific protein is produced from a gene) without having to pass the signal on to other receptors or messengers.

This illustration shows a hydrophobic signaling molecule that diffuses across the plasma membrane and binds an intracellular receptor in the cytoplasm. The intracellular receptor-signaling molecule complex then travels to the nucleus and binds DNA.
Figure 2 Hydrophobic signaling molecules typically diffuse across the plasma membrane and interact with intracellular receptors in the cytoplasm. Many intracellular receptors are transcription factors that interact with DNA in the nucleus and regulate gene expression.

Cell-Surface Receptors

Cell-surface receptors, also known as transmembrane receptors, are proteins that are found attached to the cell membrane. These receptors bind to external ligand molecules (ligands that do not travel across the cell membrane). This type of receptor spans the plasma membrane and performs signal transduction, in which an extracellular signal is converted into an intercellular signal. Ligands that interact with cell-surface receptors do not have to enter the cell that they affect. Cell-surface receptors are also called cell-specific proteins or markers because they are specific to individual cell types.

Each cell-surface receptor has three main components: an external ligand-binding domain, a hydrophobic membrane-spanning region, and an intracellular domain inside the cell. The size and extent of each of these domains vary widely, depending on the type of receptor.

Figure 3 Cell-surface receptors function by transmitting a signal through the cell membrane. The ligand does not directly enter the cell. Photo credit Laozhengzz; Wikimedia commons. 
Cell-surface receptors are involved in most of the signaling in multicellular organisms. There are three general categories of cell-surface receptors: ion channel-linked receptors, G-protein-linked receptors, and enzyme-linked receptors.

Ion channel-linked receptors

Ion channel-linked receptors bind a ligand and open a channel through the membrane that allows specific ions to pass through. To form a channel, this type of cell-surface receptor has an extensive membrane-spanning region. When a ligand binds to the extracellular region of the channel, there is a conformational change in the proteins structure that allows ions such as sodium, calcium, magnesium, and hydrogen to pass through (Figure 4).

This illustration shows a gated ion channel that is closed in the absence of a signaling molecule. When a signaling molecule binds, a pore in the middle of the channel opens, allowing ions to enter the cell.
Figure 4 Gated ion channels form a pore through the plasma membrane that opens when the signaling molecule binds. The open pore then allows ions to flow into or out of the cell.

G-protein-coupled receptors

G-protein-coupled receptors bind a ligand and activate a membrane protein called a G-protein. The activated G-protein then interacts with either an ion channel or an enzyme in the membrane (Figure 5). Before the ligand binds, the inactive G-protein can bind to a site on a specific receptor. Once the G-protein binds to the receptor, the G-protein changes shape, becomes active, and splits into two different subunits. One or both of these subunits may be able to activate other proteins as a result.

This illustration shows the activation pathway for a heterotrimeric G-protein, which has three subunits: alpha beta, and gamma, all associated with the inside of the plasma membrane. When a signaling molecule binds to a G-protein-coupled receptor in the plasma membrane, a GDP molecule associated with the alpha subunit is exchanged for GTP. The alpha subunit dissociates from the beta and gamma subunits and triggers a cellular response. Hydrolysis of GTP to GDP terminates the signal.
Figure 5 When a signaling molecule binds to a G-protein-coupled receptor in the plasma membrane, a GDP molecule associated with the G-protein is exchanged for GTP. The subunits come apart from each other, and a cellular response is triggered either by one or both of the subunits. Hydrolysis of GTP to GDP terminates the signal.

Enzyme-linked receptors

Enzyme-linked receptors are cell-surface receptors with intracellular domains that are associated with an enzyme. In some cases, the intracellular domain of the receptor itself is an enzyme. Other enzyme-linked receptors have a small intracellular domain that interacts directly with an enzyme. When a ligand binds to the extracellular domain, a signal is transferred through the membrane, activating the enzyme. Activation of the enzyme sets off a chain of events within the cell that eventually leads to a response.

How Viruses Recognize a Host

Unlike living cells, many viruses do not have a plasma membrane or any of the structures necessary to sustain life. Some viruses are simply composed of an inert protein shell containing DNA or RNA. To reproduce, viruses must invade a living cell, which serves as a host, and then take over the hosts cellular apparatus. But how does a virus recognize its host?

Viruses often bind to cell-surface receptors on the host cell. For example, the virus that causes human influenza (flu) binds specifically to receptors on membranes of cells of the respiratory system. Chemical differences in the cell-surface receptors among hosts mean that a virus that infects a specific species (for example, humans) cannot infect another species (for example, chickens).

However, viruses have very small amounts of DNA or RNA compared to humans, and, as a result, viral reproduction can occur rapidly. Viral reproduction invariably produces errors that can lead to changes in newly produced viruses; these changes mean that the viral proteins that interact with cell-surface receptors may evolve in such a way that they can bind to receptors in a new host. Such changes happen randomly and quite often in the reproductive cycle of a virus, but the changes only matter if a virus with new binding properties comes into contact with a suitable host. In the case of influenza, this situation can occur in settings where animals and people are in close contact, such as poultry and swine farms (Sigalov, 2010). Once a virus jumps to a new host, it can spread quickly. Scientists watch newly appearing viruses (called emerging viruses) closely in the hope that such monitoring can reduce the likelihood of global viral epidemics.

 

References

Text adapted from: OpenStax, Biology. OpenStax CNX. October 13, 2017. https://cnx.org/contents/GFy_h8cu@10.118:H4oMpCSi@8/Signaling-Molecules-and-Cellul#footnote1

A. B. Sigalov, The School of Nature. IV. Learning from Viruses, Self/Nonself 1, no. 4 (2010): 282-298. Y. Cao, X. Koh, L. Dong, X. Du, A. Wu, X. Ding, H. Deng, Y. Shu, J. Chen, T. Jiang, Rapid Estimation of Binding Activity of Influenza Virus Hemagglutinin to Human and Avian Receptors, PLoS One 6, no. 4 (2011): e18664.

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