2. Chemical Signals and Cellular Receptors
• Most cells have some ability to sense and respond to specific
chemical signals.
• Prokaryotes have membrane-bound receptor molecules on the cell
surface that enable them to respond to substances in their
environment.
• The human body has receptors on the tongue and in the nose that
detect chemicals in food and the air.
• Even cells of early embryos possess sophisticated machinery for
detecting changes in their surroundings.
3. Chemical Signals and Cellular Receptors
• Cells also produce signals. One way they do this is by displaying molecules
on their surfaces that are recognized by receptors on the surfaces of other
cells.
• This kind of cell-to-cell communication requires direct physical contact
between cells.
• Alternatively, one cell can release chemical signals that are recognized by
another cell, either nearby or at a distant location.
• In complex multicellular organisms, the problem of regulating and
coordinating the various activities of cells or tissues is particularly
important because the whole organism is organized into different tissues
made up of specialized cells.
4. Chemical Signaling Involves Several Key
Components
Short- Versus Long-Range Signals.
• A variety of compounds can function as chemical messengers.
• Signaling molecules are often classified based on the distance
between their site of production and the target tissue(s) upon which
they act.
• Some messengers, such as hormones, act as endocrine signals.
• They are produced at great distances from their target tissues and are
carried by the circulatory system to various sites in the body.
5. • Other signals, such as growth factors, are released locally, where they
diffuse to act at short range on nearby tissues.
• Such signals are referred to as paracrine signals.
• When signals are passed at such short range that they require
physical contact between the sending and receiving cells, they are
said to be juxtacrine signals.
• Still other local mediators act on the same cell that produces them;
such signals are called autocrine signals.
6.
7. Receptors and Ligands.
• Once a messenger reaches its target tissue, it binds to receptors on
the surface of the target cells, initiating the signaling process.
• A molecule coming from either a long or a short distance functions as
a ligand by binding to a receptor.
• A ligand often binds to a receptor embedded within the plasma
membrane of the cell receiving the signal.
• In other cases, the ligand binds to a receptor inside the cell.
8.
9. Signal Transduction.
• Binding of a ligand to its receptor is just the first step in cell-cell
signaling.
• In this sense, the ligand is a “primary messenger.”
• The binding of ligand to receptor often results in the production of
additional molecules or ions within the cell receiving the signal, which
is how a cell is able to “sense” that the appropriate ligand has
successfully bound to the receptor.
10. • Such second messengers relay the signals from one location in the
cell, such as the plasma membrane, to the interior of the cell,
initiating a cascade of changes within the receiving cell.
• Often these events affect the expression of specific genes within the
receiving cell.
• The ultimate result is a change in the identity or function of the cell.
• The ability of a cell to translate a receptor-ligand interaction to
changes in its behavior or gene expression is known as signal
transduction.
11. G Protein-Coupled Receptors
• The G protein-coupled receptors (GPCRs) are so named because
ligand binding causes a change in receptor conformation that
activates a particular G protein (an abbreviation for guanine-
nucleotide binding protein).
• A portion of the activated G protein in turn binds to a target protein,
such as an enzyme or a channel protein, thereby altering the target’s
activity.
• Examples of GPCRs include olfactory receptors (responsible for our
sense of smell), β-adrenergic receptors, and hormone receptors such
as those for thyroid-stimulating hormone and follicle-stimulating
hormone.
12. The Structure and Regulation of GPCRs
• The receptor forms seven transmembrane α helices connected by
alternating cytosolic or extracellular loops.
• The N-terminus of the protein is exposed to the extracellular fluid,
whereas the C-terminus resides in the cytosol.
• The extracellular portion of each GPCR has a unique messenger-
binding site, and the cytosolic loops allow the receptor to interact
with only certain types of G proteins.
13.
14.
15. Cyclic AMP Is a Second Messenger Whose
Production Is Regulated by Some G Proteins
• Cyclic AMP (cAMP) is formed from cytosolic ATP by the enzyme
adenylyl cyclase.
• Adenylyl cyclase is anchored in the plasma membrane, with its
catalytic portion protruding into the cytosol.
• Normally, the enzyme is inactive until it binds to an activated Gα
subunit of a specific G protein, such as Gs. When a GPCR is coupled to
Gs, the binding of ligand stimulates the Gsα subunit to release GDP
and acquire a GTP.
• This in turn causes GTP- G𝑠𝛼 to detach from the G𝑠 𝛽𝛾 subunits and
bind to adenylyl cyclase. When GTP- G𝑠 binds to adenylyl cyclase, the
enzyme becomes active and converts ATP to cAMP.
16.
17.
18. Many G Proteins Act Through Inositol
Trisphosphate and Diacylglycerol
• Inositol-1,4,5-trisphosphate (IP3), one of the breakdown products of
inositol phospholipids, functions as a second messenger.
• IP3 is generated from phosphatidylinositol-4, 5-bisphosphate (PIP2),a
relatively uncommon membrane phospholipid, when the enzyme
phospholipase C is activated.
• Phospholipase C cleaves PIP2 into two molecules—inositol
trisphosphate and diacylglycerol (DAG).
• IP3 and DAG were shown to be second messengers in a variety of
regulated cell functions.
19.
20. The Release of Calcium Ions Is a Key Event
in Many Signaling Processes
• Normally, the concentration of calcium is maintained at very low levels in
the cytosol due to the presence of calcium ATPases (pumps) in the plasma
membrane and the ER.
1. Calcium ATPases in the plasma membrane transport calcium out of the
cell, whereas
2. the calcium ATPases in the ER sequester calcium ions in the lumen of the
ER.
3. In addition, some cells have sodium-calcium exchangers that further
reduce the cytosolic calcium concentration.
4. Finally,mitochondria can transport calcium into the mitochondrial matrix.
21.
22. Enzyme-Coupled Receptors
• These proteins not only function as receptors but also are themselves
enzymes, the most common being protein kinases.
• When these receptor kinases bind to the appropriate ligand, their
kinase activity is stimulated, and they transmit signals through a
cascade of phosphorylation events within the cell.
• Kinases are enzymes that add phosphate groups to particular amino
acids within substrate proteins.
