Topic 5.

6: The Plasma Membrane Plays A Key Role In Most Cell Signaling

➢​ Unicellular organisms (including prokaryotes) need cell communication.
Local and Long Distance Signaling
➢​ Eukaryotic cells may communicate by direct contact, a type of local signaling.
➢​ Both animal and plant cells have cell junctions that connect the cytoplasm of near-by
cells.
○​ Animal: Gap Junctions
○​ Plants: Plasmodesmata
➢​ Signaling substances that are dissolved in the cytosol can pass freely with the cells
close.
➢​ Animal cells may communicate via direct contact between membrane-bound
cell-surface molecules in cell to cell recognition.
➢​ In local signaling, the signaling cell (ligand) creates messenger molecules. These only
travel short distances .
○​ Growth Factors: Compounds that stimulate target cells close to grow and
divide.
○​ Paracrine Signaling: A secreting cell acts on nearby target cells by secreting
molecules of a local regulator.
○​ Synaptic Signaling: A nerve cell releases neurotransmitter moles into a
synapse, stimulating the target cell (like a muscle or nerve cell).
➢​ Hormones: Chemical messengers for long-distance signaling.
○​ Vary in shape and size
➢​ Endocrine Signaling: Specialized endocrine cells secrete hormones into body fluids.
Hormones can reach almost all body cells, but are only bound to some cells.

The Three Stages of Cell Signaling: A Preview

➢​ Reception
○​ Is the target cell’s detection of a signaling molecule coming from outside of the
cell. A chemical signal is “detected” when the signaling molecule binds to a
receptor protein located at the cell's surface or inside the cell.
 ➢​ Transduction
○​ A step or series of steps that converts the signal to a form that can bring about
a specific cellular response. Transduction requires a sequence of changes in a
series of different molecules -- a signal transduction pathway. These molecules
in the pathway are often called relay molecules.
➢​ Response
○​ The transduced signal triggers a specific cellular response. The response can be
any cellular activity like a catalysis by an enzyme rearrangement of the
cytoskeleton or activation of specific genes in the nucleus. The cell-signaling
process helps make sure that crucial activities occur in the right cells, at the
right time and in proper coordination with the activities of other cells of the
organism.
Reception: the Binding of a Signaling Molecule to a Receptor Protein
➢​ A receptor protein honor and the target cell allows the cell to detect the signal and
respond to it
➢​ The signaling molecule is complementary and shaped to a specific site on the
receptor and attaches there ( similar to an enzyme).
➢​ The signaling molecule acts as a ligand which is a molecule that specifically binds to
another molecule which is usually a larger one.
○​ Ligand binding generally causes a receptor protein to undergo a change in
shape.
■​ The shape change directly activates the receptor which enables it to
interact with other cellular molecules.
➢​ Most signal receptors are plasma membrane proteins. Their ligands are water soluble
and are usually too large to pass freely through the plasma membrane.
Receptors in the Plasma Membrane
➢​ Most water soluble signaling molecules bind to specific sites on receptor proteins that
span the cell's plasma membrane.
➢​ A transmembrane receptor transmits information by the extracellular movement to
the inside of the cell by changing shape when a specific ligand binds to it.
➢​ G Protein Coupled Receptors
○​ A GPCR is a cell surface transmembrane receptor that works with the help of a
g protein which is a protein that binds to the energy rich molecule GTP ( similar
to ATP). These receptors vary in The Binding site for their signaling molecules
and for different types of G proteins inside the cell. GPCRs are similar in
structure which suggests that these signaling systems evolved early.
○​ GPCR Pathways are extremely diverse in their functions which include the rules
and embryo bionic development and in the senses of sight, smell and taste.
○​ GCPR is also involved in many human diseases such as cholera and pertussis.
➢​ Ligand Gated Ion Channel
○​ A ligand gated ion channel is a membrane receptor with a region that can act as
a gate for ions when the receptor assumes a certain shape.
 ○​ When a signaling molecule binds as a ligand to the receptor protein the gate
opens or closes which allows or blocks the diffusion of specific ions such as Na+
or CA2+ through a channel and the protein.
○​ like and gated ion channels are very important in the nervous system.
■​ Then neurotransmitter molecules released at a synapse between two
nerve cells bind as ligands to ion channels on the receiving cell which
causes the channels to open. The diffusion of ions through the open
channels may trigger an electrical signal that propagates down the
length of the receiving cell.
Intracellular Receptors
➢​ Intracellular receptor proteins are found in either the cytoplasm or nucleus of target
cells.
➢​ To reach a receptor a signaling molecule passes through the target cell's plasma
membrane.
○​ Many signaling molecules can do this because they are hydrophobic enough to
cross that hydrophobic interior of
the membrane.
○​ These hydrophobic chemical
Messengers include steroid
hormones and thyroid hormones of
animals.
○​ In both animals and plants another
chemical signaling molecule with
an intracellular receptor is nitric
oxide (NO) which is a gas and its
very small hydrophobic molecules
which can easily pass between the
membrane phospholipids.
➢​ Genes in a cell’s DNA function by being
transcribed and processed into
messenger RNA (mRNA), which leaves
the nucleus and is translated into a
specific protein by ribosomes in the
cytoplasm.
➢​ Transcription Factors control which
genes are turned on (which genes are transcribed into mRNA in a particular cell at a
particular time. When the aldosterone receptor is activated, it acts as a transcription
factor that turns on specific genes.)

Transduction by Cascades of Molecular Interactions

 ➢​ When receptors for signaling molecules are plasma membrane proteins, the
transduction stage of cell signaling is usually a multistep pathway involving many
molecules.
○​ Activation of proteins by addition or removal of phosphate groups or release of
other small molecules or ions that act as messengers.
○​ A benefit of the multiple steps is the possibility of greatly amplifying a signal.
Each molecule in a pathway transmits the signal to numerous molecules at the
next step in the series, the result is a geometric increase in the number of
activated molecules by the end of the pathway.
○​ Multistep pathways provide more opportunities for coordination and control
than do simpler systems.
➢​ The binding of a specific signaling molecule to a receptor in the plasma membrane
triggers the first step in the chain of molecular interactions-the signal transduction
pathway-that leads to a particular response within the cell. The signal-activated
receptor activates another molecule, which activates yet another molecule, and so
on, until the protein that produces the final cellular response is activated. The
molecules that relay a signal from receptor to response, which we call relay molecules
in this book, are often proteins. The original signaling molecule is not physically
passed along a signaling pathway; in most cases, it never even enters the cell. When
we say that the signal is relayed along a pathway, we mean that certain information is
passed on. At each step, the signal is transduced into a different form, usually by a
shape change in a protein. Often, the shape change is brought about by
phosphorylation (the addition of phosphate groups to a protein).
Protein Phosphorylation and Dephosphorylation
➢​ An enzyme that transfers phosphate groups from ATP to a protein is known as a
protein kinase.
○​ Such enzymes are widely involved in signaling pathways in animals, plants, and
fungi.
○​ Many of the relay molecules in signal transduction pathways are protein
kinases, and they often act on other protein kinases in the pathway. A
hypothetical pathway containing two different protein kinases that form a short
phosphorylation cascade. The sequence shown is similar to many known
pathways, although typically three protein kinases are involved. The signal is
transmitted by a cascade of protein phosphorylations, each bringing with it a
shape change. Each such shape change results from the interaction of the
newly added phosphate groups with charged or polar amino acids. The addition
of phosphate groups often changes the form of a protein from inactive to
active.
➢​ Protein Phosphatases are enzymes that can rapidly remove phosphate groups from
proteins, which is called dephosphorylation.
 ➢​ By dephosphorylation and inactivating protein kinases, the phosphates provide the
mechanism for turning off the signal transduction pathway when the initial signal is
no longer present.
➢​ Phosphates make the protein kinases reusable which enables the cell to respond
again to an extracellular signal.
➢​ A phosphorylation-dephosphorylation system is like a molecular switch in the cell
which turns on an activity on or off as required.
➢​ The activity of a protein regulated by phosphorylation depends on the balance in the
cell between the active kinase molecules and the active phosphate molecules.
Small Molecules and Ions as Second
Messengers
➢​ Many signaling pathways also involve small,
nonprotein, water soluble molecules or ions
called second messengers.
➢​ The small second messengers can readily
spread throughout the cell by diffusion. The
two most common second messengers are
cyclic AMP and calcium ions, Ca2+.
Response: Regulation of Transcription or
Cytoplasmic Activities
➢​ A signal transduction pathway leads to the
regulation of one or more cellular activities.
➢​ The response occurs in the nucleus of the
cell or in the cytoplasm.
➢​ Many signaling pathways ultimately regulate protein
➢​ synthesis, usually by turning specific genes on or off in the
➢​ nucleus. Like an activated steroid receptor the final activated molecule in a signaling
pathway may function as a transcription factor.
➢​ The response to this growth factor signal is transcription (the synthesis of one or
more specific mRNAs, which will be translated into the cytoplasm into specific
proteins.
➢​ Sometimes, the transcription factor might regulate a gene by turning it off. Often a
transcription factor regulates several different genes.
➢​ Sometimes a signaling pathway may regulate the activity of proteins rather than
causing their synthesis by activating gene expression.
➢​ This directly affects proteins that function outside the nucleus. For example, a signal
may cause the opening or closing of an ion channel in the plasma membrane or a
change in cell metabolism. The response of cells to the hormone epinephrine helps
regulate cellular energy metabolism by affecting the activity of an enzyme: The final
step in the signaling pathway that begins with epinephrine binding activates the
enzyme that catalyzes the breakdown of glycogen.