A sudden noise makes your heart pound before you've even worked out what it was. Your sympathetic nerves and adrenal glands have responded. Epinephrine (adrenaline) from the adrenal glands also reaches your liver, and liver cells start releasing glucose into your blood. In the 1950s Earl Sutherland asked how a hormone that never enters the liver cell could change what happens inside it. His answer, a second messenger called cyclic AMP, earned him the 1971 Nobel Prize, and it's the heart of this unit.
How cells communicate
Cells signal each other in three main ways:
- Direct contact: neighboring cells pass molecules through junctions, or touch surface molecules.
- Local signaling: a cell releases a signal that acts on nearby cells, such as neurotransmitters crossing a synapse.
- Long-distance signaling: hormones travel in the blood to target cells anywhere in the body.
A signaling molecule is called a ligand. It acts only on cells with a receptor that fits it.
Signal transduction
Every signaling pathway has three stages:
- Reception: the ligand binds a receptor, often on the cell membrane. A common type is the G protein-coupled receptor (GPCR), which switches on a G protein inside the cell. Epinephrine's receptor is one.
- Transduction: the receptor changes shape and passes the signal along a chain of molecules inside the cell. Second messengers such as cAMP spread it. Protein kinases add phosphate groups to other proteins in a phosphorylation cascade.
- Response: the cell does something, such as switching on genes, opening channels or releasing glucose.
Each step can activate many molecules at the next, so one ligand can produce a huge response. That's amplification.
When signaling goes wrong
A mutation in a receptor or a relay protein can block a pathway or leave it stuck on. A pathway stuck on can tell a cell to divide when it shouldn't, which is one route to cancer. Drugs often work by blocking a receptor or an enzyme in a pathway.
Feedback
- Negative feedback reverses a change and keeps conditions steady. When blood glucose rises, insulin brings it down. When it falls, glucagon brings it up.
- Positive feedback amplifies a change until an endpoint. During childbirth, oxytocin increases contractions, which trigger more oxytocin. Ethylene triggers ripening, and ripening fruit makes more ethylene, so ripening speeds up and spreads to nearby fruit.
The cell cycle
- Interphase takes most of the cycle. In G1 the cell grows. In S it replicates its DNA. In G2 it prepares to divide.
- Mitosis divides the copied chromosomes: prophase, metaphase, anaphase, telophase.
- Cytokinesis splits the cytoplasm into two daughter cells.
Some cells, such as most mature neurons, leave the cycle and enter G0, where they no longer divide.
Regulating the cycle
Checkpoints at G1, G2 and M stop the cycle if something's wrong, such as damaged DNA or chromosomes not attached to the spindle. The cycle is driven by cyclins, proteins whose levels rise and fall, and cyclin-dependent kinases (CDKs), which are active only when bound to a cyclin.
When checkpoints fail, cells can divide uncontrollably and form tumors. Cells that are too damaged to repair can undergo apoptosis, programmed cell death.
Common mistakes students make
- Saying the hormone enters the cell. Many ligands, like epinephrine, never cross the membrane. They act through receptors and second messengers.
- Calling all feedback negative. Positive feedback is real; it just ends at an endpoint, like birth.
- Putting DNA replication in mitosis. DNA is copied in S phase, before mitosis begins.
- Thinking cyclins are enzymes. CDKs are the enzymes; cyclins activate them.
Frequently asked questions
What are the three stages of cell signaling?
Reception, transduction and response.
What is the difference between positive and negative feedback?
Negative feedback reverses a change to keep conditions stable. Positive feedback amplifies a change until an endpoint is reached.
What do cyclins and CDKs do?
Cyclins bind and activate cyclin-dependent kinases, which push the cell through the checkpoints of the cell cycle.
What happens if a cell cycle checkpoint fails?
Cells can divide when they shouldn't, which can lead to cancer.
Try it
Say each answer before you flip the card. Then predict: what would you expect to see if a liver cell's receptor for epinephrine were missing?
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