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Chapter 9 · Part 4 of 10
  1. Chapter overview
  2. 1Why cells communicate
  3. 2The three stages of cell signaling
  4. 3How receptors recognize signals
  5. 4Four kinds of receptors
  6. 5How a growth factor tells a cell to divide
  7. 6Second messengers and the fight-or-flight response
  8. 7Amplifying, ending, and combining signals
  9. 8One hormone, many responses
  10. 9Programmed cell death
  11. 10How apoptosis is triggered

Four kinds of receptors

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Receptors differ in where they sit and in what they do once a ligand, the signaling molecule that fits them, switches them on. Most cell surface receptors fall into three types: enzyme-linked receptors, G-protein-coupled receptors, and ligand-gated ion channels. Intracellular receptors make a fourth.

Enzyme-linked receptors

Some receptors are enzymes themselves, able to speed up a chemical reaction. These enzyme-linked receptors occur in all living species. Each typically has two working regions, or domains: an outer one that binds the signal and an inner one that does the enzyme’s job. When the signal binds, the shape change passes through the membrane-crossing part of the protein and switches on the inner domain, much as turning a doorknob moves the latch on the other side of the door.

Insulin is one of many human hormones that use these receptors: when it binds its receptor on muscle cells, the cells get better at using glucose.

Many enzyme-linked receptors are protein kinases, enzymes that move a phosphate group from ATP onto a specific amino acid in a protein. (ATP is the molecule cells use to carry energy; a phosphate group is a small cluster of phosphorus and oxygen atoms with a negative charge.) Adding a phosphate this way is phosphorylation.

Tyrosine kinases attach phosphate to the amino acid tyrosine, and serine/threonine kinases attach it to serine or threonine. The phosphate’s negative charge reshapes the protein it lands on, which changes how that protein works. An activated receptor kinase may phosphorylate itself, other proteins inside the cell, or both.

G-protein-coupled receptors

Other receptors hand the signal to a partner inside the cell, a G protein, which a lipid anchors to the inner face of the membrane. These are G-protein-coupled receptors (GPCRs). A GPCR typically crosses the plasma membrane seven times, weaving back and forth like a stitch.

GPCRs occur in all eukaryotes (organisms whose cells have a nucleus) and are especially common in animals. Humans have about 1,000 genes for them, with roles in vision, smell, behavior, and more.

G proteins are named for the molecules they hold: GTP, which is like ATP but made with guanine instead of adenine, or GDP, which is GTP minus one phosphate group. A G protein has three subunits, separate protein chains called α (alpha), β (beta), and γ (gamma).

  1. A signaling molecule binds the GPCR, which changes shape and becomes active.
  2. The active GPCR binds a G protein.
  3. The G protein releases GDP and picks up GTP instead.
  4. GTP changes the G protein’s shape, and it splits into two parts: the α subunit and the β/γ dimer (a dimer is two joined subunits, here β and γ).
  5. The α subunit goes on to activate other proteins in a signal transduction pathway. The β/γ dimer can pass the signal on too, for example by regulating ion channels.

Shutting down takes two events. First, the signaling molecule comes off, so the GPCR switches off and the response reverses. Second, the α subunit hydrolyzes its GTP, using water to split it into GDP and phosphate; only then can it rejoin the β/γ dimer as an inactive G protein. GTP means on; GDP means off.

Signaling molecule γ β α GDP GTP Extracellular fluid Plasma membrane Cytosol GPCR G protein α subunit β/γ dimer
Figure 9.3 A signaling molecule binds the GPCR, and the active GPCR binds the G protein. The G protein then swaps GDP for GTP, and that swap is what activates it. The active G protein splits into the α subunit, carrying GTP, and the β/γ dimer.

Ligand-gated ion channels

Ions (atoms or molecules with an electric charge, such as sodium ions, Na⁺) can’t cross the oily core of a membrane on their own. They move through ion channels, protein tunnels that let specific ions pass. A ligand-gated ion channel, also called an ionotropic receptor, is a channel that opens only when its ligand binds. Ions then flow through, raising or lowering their concentration inside the cell.

These receptors occur in animal, plant, and fungal cells. Animals use them to pass signals from nerve cells to muscle cells and from one nerve cell to the next. The acetylcholine receptor on skeletal muscle cells is one: when acetylcholine, a neurotransmitter released by a neighboring nerve cell, binds, the channel opens and Na⁺ flows through.

Intracellular receptors

Steroid hormones such as estrogen are hydrophobic, so they diffuse (drift) straight through the plasma membrane. In vertebrates (animals with backbones), the receptors for steroid hormones are inside the cell. Some wait in the cytosol and move into the nucleus after binding. The estrogen receptor is already in the nucleus.

  1. Estrogen, released into the blood by an endocrine gland, diffuses through the plasma membrane of a target cell.
  2. In the nucleus, estrogen binds a receptor subunit, which changes shape.
  3. Two estrogen-bound subunits join to form a dimer, the active receptor.
  4. The dimer binds to DNA and turns on transcription of specific genes.

Because it turns genes on, the estrogen receptor is a transcription factor. It has two key sites, one that binds estrogen and one that binds DNA, and the DNA-binding site works only after estrogen has bound. With the receptor acting on genes directly, no signal transduction pathway is needed.

The four types compared

Receptor type Location What activation does Example
Enzyme-linked receptor Plasma membrane Phosphorylates an intracellular protein EGF receptor
G-protein-coupled receptor Plasma membrane Activates a G protein Epinephrine receptor
Ligand-gated ion channel Plasma membrane Opens an ion channel Acetylcholine receptor
Intracellular receptor Cytosol or nucleus Turns on transcription of specific genes Estrogen receptor
Check yourselfA mutation makes a G protein’s α subunit bind so tightly to the β/γ dimer that the two can’t separate. How would this affect the cell’s response to the GPCR’s signal?

The α subunit couldn’t break away to activate the next protein in the pathway. The signal transduction pathway wouldn’t be activated, so the cellular response would be blocked or weakened.

Practice questions

  1. 1 of 2

    Acetylcholine binds its receptor, a ligand-gated ion channel, on a skeletal muscle cell. What happens next?

  2. 2 of 2

    Which of these receptors is found inside the cell rather than in the plasma membrane?