CHAPTER SUMMARY
9.1 CELLS COMMUNICATE PRIMARILY BY SENDING AND RECEIVING CHEMICAL SIGNALS.
- There are four essential players in communication between two cells: a signaling cell, a signaling molecule, a receptor, and a responding cell.
- The signaling molecule binds to its receptor on the responding cell, leading to receptor activation, signal transduction and amplification, response, and eventually termination of the signal and response.
9.2 CELL SIGNALING CAN BE CLASSIFIED ACCORDING TO THE DISTANCE BETWEEN THE SIGNALING AND RESPONDING CELLS.
- Endocrine signaling takes place over long distances and relies on the circulatory system for delivery of signaling molecules.
- Paracrine signaling takes place over short distances between neighboring cells.
- Autocrine signaling occurs when a cell signals itself.
- Juxtacrine communication depends on physical contact between cells.
9.3 SIGNALING MOLECULES BIND TO AND ACTIVATE SPECIFIC CELL-SURFACE AND INTRACELLULAR RECEPTORS.
- A signaling molecule, or ligand, binds to the ligand-binding site of the receptor. Binding causes the receptor to undergo a conformational change that activates the receptor.
- Receptors for polar signaling molecules, including growth factors, are located on the plasma membrane.
- Receptors for nonpolar signaling molecules, such as steroid hormones, are located in the cytosol or in the nucleus.
- There are three major types of cell-surface receptor: G protein-coupled receptors, receptor kinases, and ligand-gated ion channels. All act as molecular switches.
- G protein-coupled receptors associate with G proteins, which are active when bound to GTP and inactive when bound to GDP.
- Receptor kinases are activated by phosphorylation and inactivated by dephosphorylation.
- Ligand-gated ion channels open in response to a signal, allowing the movement of ions across the plasma membrane.
9.4 SIGNALS ARE TRANSMITTED ACROSS THE PLASMA MEMBRANE AND ARE OFTEN AMPLIFIED IN THE CYTOSOL, LEADING TO A CELLULAR RESPONSE FOLLOWED BY TERMINATION.
- G proteins are associated with G protein-coupled receptors that bind signaling molecules.
- G proteins are composed of three subunits, denoted α, β, and γ. When a G protein encounters an activated receptor, the α subunit exchanges GDP for GTP, dissociates from the β and γ subunits, and becomes active.
- Second messengers like cAMP amplify the signal in the cytosol (brought to the cell by the extracellular first messenger).
- Intracellular, cytosolic signals are short-lived before they are terminated.
- Ligand binding to a receptor kinase causes it to dimerize with another receptor bound to the same ligand. The two receptor kinases become active when they phosphorylate each other’s cytoplasmic domains, allowing activation of intracellular signaling pathways.
- The phosphorylated receptors are bound by other proteins, which cause the subsequent activation of other cytosolic signaling molecules, such as Ras.
- When Ras is activated, the GDP to which it is bound is released and is replaced by GTP. The active, GTP-bound Ras temporarily binds to and activates the first in a series of kinases.
- Neurons communicate with other neurons and with muscle cells using ligand-gated ion channels, which lead to movement of ions across the membrane and a change in the membrane charge or potential.
- Cancer can be caused by malfunction of any step in the signaling processes involved in cell division.
- Mutations in receptor kinases and Ras are frequently associated with human cancers.
- Several signaling pathways can take place simultaneously in a single cell, and the cellular response depends on the integration of several signals.
9-17
Self-Assessment Question 1
Name the four players in cell communication.
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Model Answer:
The four players in cell communication are a signaling cell, a signaling molecule, a receptor molecule, and a responding cell.
Self-Assessment Question 2
Name the steps that are often involved in cell communication.
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Model Answer:
The steps involved in cell communication are receptor activation, signal transduction, response, and termination.
Self-Assessment Question 3
Describe one way in which endocrine-, paracrine-, autocrine-, and juxtacrine-signaling pathways are similar to one another and one way they differ from one another.
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Model Answer:
One way in which the signaling pathways are similar is that the steps involved in the signaling cascade are the same (ie receptor activation, signal transduction, response and termination). One difference between the pathways is the distance between the signaling and responding cell. Another difference is the nature of the signaling molecule and whether it’s a small molecule or transmembrane protein.
Self-Assessment Question 4
Explain how cells respond to external signals even when those signals cannot enter the cell.
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Model Answer:
Cells can respond to external signals by utilizing specific transmembrane proteins called receptors that bind to the signal (ligand) via the receptor’s specific ligand-binding site. The binding of ligand to its receptor causes a conformational change in the receptor, activating it. The activated receptor transmits the signal inside the cell, generating a response. The type of ligand and receptor determine how the cell will respond to the signal.
Self-Assessment Question 5
Explain how signals can be specific in targeting only some cells, even if they are released into the bloodstream and come into contact with many cells.
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Model Answer:
A signal can be specific for a particular cell type even if the signal is in the bloodstream because the signal will only recognize receptors with a binding site specific for that signal. These receptors are not present on every cell; different cell types express a different assortment of receptor types on their surface. In this way, only a subset of cells will respond to any given signal, even if that signal is present throughout the organism.
Self-Assessment Question 6
List several possible types of responses a cell might have to a signaling molecule.
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Model Answer:
Several possible types of responses a cell might have to a signaling molecule are migration of the cell to another part of the body, activation of a particular protein, shape change of the cell itself, growth (cell division), production of defensive enzymes, self-destruction (apoptosis), and differentiation, to name a few.
Self-Assessment Question 7
Compare and contrast cell-surface receptors and intracellular receptors in terms of their location, chemical properties of their signaling molecules, and types of responses mediated.
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Model Answer:
Cell-surface receptors are usually transmembrane proteins with an extracellular domain, transmembrane domain, and cytoplasmic domain. They are specific for polar signaling molecules that cannot diffuse across the membrane; these polar ligands bind with the receptor in the extracellular matrix (outside the cell). The receptor then transmits the signal to the inside of the cell, leading to a cellular response which could be the activation of an enzyme, or transcription of a particular gene, for example. Intracellular receptors exist inside the cell, either in the cytoplasm or in the nucleus itself. Their signaling molecules are typically nonpolar and can easily diffuse through the cell membrane. Once inside the cell, the ligand binds with its receptor, causing the receptor to change shape; in the case of steroid signals, the ligand receptor complex moves into the nucleus if it is not there already, to activate specific gene transcription.
Self-Assessment Question 8
List several ways in which a signal may be amplified in an intracellular signaling pathway.
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Model Answer:
In the example of G-protein—coupled receptors, a signal is amplified in several ways. A single activated G-protein coupled receptor can activate multiple G-proteins. Each active G-protein activates an adenylyl cyclase molecule, each of which generates a large amount of cAMP. Each cAMP molecule activates a molecule of protein kinase A (PKA). Once activated, each PKA enzyme phosphorylates and activates multiple protein targets. See Figure 9.10.
Self-Assessment Question 9
Describe ways in which the response of a cell to a signal can be terminated.
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Model Answer:
Response of a cell to a signal can be terminated at a variety of levels. The receptor itself could change its conformation to the inactive form, the protein interacting with the intracellular portion of the receptor could become inactivated (perhaps due to de-phosphorylation) or any of the downstream enzymes (like cAMP or Protein kinase A) could become inactivated.