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Cell Signaling
Apoptosis, which can be induced by signals
from other cells, is the process by which
cells do which of the following?
A) Move to other parts of the cell (migrate).
B) Take on different shapes (morphology)
C) Express different genes to take on their
final function.
D) Kill themselves through programmed cell
death
E) Eat (phagocytose) other cells
Why Cell Signaling?
• Cell communication is the process of cells
detecting and responding to signals in the
extracellular environment
• Needed to coordinate cellular activities in a
multicellular organism
• Apoptosis is caused by signals that intentionally
cause a cell to die
Why Cell Signaling?
• Cell communication or cell signaling involves
incoming and outgoing signals
• Signals are agents that influence the properties of
cells
– cAMP
– Growth Factors
– Hormones
• Signals affect the conformation of a receptor (ie a
membrane protein) leading to a response inside the
cell
Why do cells need to respond to
signals?
1. Need to respond to a changing environment
– Adaptation or a cellular response is critical for
survival
– Glucose acts as a signal to yeast cells to increase
number of glucose transporters and enzymes
allowing efficient uptake and use of glucose
Why do cells need to respond to
signals?
2. Cells need to communicate with each other
– Cell-to-cell communication
• Auxin is a signaling molecule transmitted from cell to
cell and inhibited by the light
Five Modes of Cell Communication
1. Direct intercellular signaling
– Cell junctions allow signaling molecules to pass
from one cell to another.
2. Contact-dependent signaling
– Some molecules are bound to the surface of cells
and serve as signals to the cell coming in contact
with them.
3. Autocrine signaling
– Cells secrete signaling molecules that bind to their
own cell surface or neighboring cells of the same
type.
Five Modes of Cell Communication (cont)
4. Paracrine signaling
– Signal does not affect cell secreting the signal
but does influence cells in close proximity
(synaptic signaling).
5. Endocrine signaling
– Signals (hormones) travel long distances and are
usually longer lasting.
Five Modes of Cell Communication
3 stages of cell signaling
1. Receptor activation
– Signaling molecule binds to receptor
2. Signal transduction/amplification
– Activated receptor stimulates sequence of
changes- signal transduction pathway
– This can also be used to amplify the signal
3. Cellular response
– Several different responses
•
•
•
Alter activity of 1 or more enzymes
Alter structural protein function
Change gene expression– transcription factor
Ligand
• Signaling molecule
• Binds noncovalently to receptor with high
degree of specificity
• Binding and release between receptor and
ligand relatively rapid
• Ligands alter receptor structureconformational change
• Once a ligand is released, the receptor is no
longer activated
Cell surface receptors
1. Enzyme-linked receptors
– Extracellular domain binds signal
– Causes intracellular domain to become
functional catalyst
– Most are protein kinases
G-protein coupled receptors (GPCR)
2. G-protein coupled receptors (GPCR)
–
–
–
–
–
–
Found in all eukaryotes, common in animals
7 transmembrane segments
Activated receptor binds to G protein
Releases GDP and binds GTP instead
GTP causes G protein to disassociate
α subunit and β/γ dimer interact with other
proteins in a signaling pathway
3. Ligand-gated ion channels
– Plant and animal cells
– Ligand binding causes ion channels to open and
ions to flow through the membrane
– Animals- signals between nerve and muscle cells or
between 2 nerve cells
4. Receptor tyrosine kinases (RTKs)
• Category of enzyme-linked receptors found in
animals
• Recognize various types of signaling molecules
– Growth factor – hormone that acts to stimulate
cell growth or division
• Epidermal Growth Factor (EGF)
– Stimulates epidermal cells to divide
Epidermal Growth Factor Receptor Pathway
Question 5
Receptor tyrosine kinases are found in which
of the following?
A) Bacteria
B) Archaea
C) Animals
D) Plants
E) All of the above
Second Messengers
• Signals binding to cell surface are first
messenger
• Many signal transduction pathways lead to
production of second messengers
– Relay signals inside cells
– Examples
• cAMP
• Ca2+
• Diacylglycerol and inositol triphosphate
Signal transduction via cAMP
• Cyclic adenosine monophosphate
• Signal binding to GPCR activates G protein to
bind GTP causing dissociation
• α subunit binds to adenylyl cyclase stimulating
synthesis of cAMP
Norepinephrine is a hormone that is
released into the blood when the adrenal
gland is stimulated by the sympathetic
preganglionic neurons. What type of
signaling effect is does this represent?
A) Endocrine
B) Paracrine
C) Synaptic
D) Contact Dependent
Signal transduction via cAMP
• One effect of cAMP is to activate protein kinase A
(PKA)
• Activated catalytic PKA subunits phosphorylates
specific cellular proteins
• When signaling molecules no longer produced,
eventually effects of PKA reversed
Signal transduction via cAMP
25
cAMP has 2 advantages
1. Signal amplification
– Binding of signal to single receptor can cause the
synthesis of many cAMP that activate PKA, each
PKA can phosphorylate many proteins
2. Speed
– A substantial amount of cAMP can be made
within 20 seconds after addition of eipnepherine
Signal amplification via cAMP
Hormonal signaling
• Type of cellular response
caused by a given
signaling molecule
depends in the type of
cell responding to the
signal
• Variation in response
determined by types of
proteins that each cell
makes
A cell’s response to hormones and
other signaling molecules depends
on which proteins it makes
• One hormone causes different effects in different
cell types
• Differential gene expression- all cells contain the
same genome but only express particular parts
• Can effect cellular response in a variety of ways
– Receptor not expressed, different receptors for same
signal, different affinities for signal, signal transduction
pathways different, protein expression different
Epinephrine example
•
•
•
•
Fight-or-flight hormone
Different effects throughout body
Stimulates heart muscle cells to beat faster
Caffeine inhibits phosphodiesterase
– Enzyme removes cAMP once a signaling molecule is
no longer present
– Inhibition causes cAMP to persist for longer so heart
beats faster
Cell-Cell Junctions
31
Anchoring
junctions
(animal
cell)
• Attach
cells to each
other and
to the ECM
• Rely on cell adhesion molecules (CAM)
– Cadherin and integrin
• 4 main categories
1.
2.
3.
4.
Adherins junctions
Desmosomes
Hemidesmosomes
Focal adhesions
33
Tight junctions in animals
•
•
•
•
Or occluding junctions
Forms tight seal between adjacent cells
Prevents ECM from leaking between cells
Tight junctions
– Made by occludin and claudin
– Bind to each to form tight seal
– Not mechanically strong, not bound to cytoskeleton
Tight junctions in animals
Gap junctions in animals
• Small gap between plasma membranes of cells at
junction
• Six connexin proteins in one cell align with six
connexin proteins in an adjacent cell to form a
connexon
• Connexon allows passage of ions and small
molecules
• Allow adjacent cell to share metabolites and directly
signal each other
Gap junctions in animals
Plasmodesmata in plants
• Functionally similar to gap junctions
• Allow passage of ions and molecules between
adjacent cells
• Different in that they are open channels where
the cell membrane of one cell is continuous with
adjacent cell membrane
• Desmotubule connects ER membrane of adjacent
cells
Plasmodesmata in plants
Question 9
Cardiac cells contain ____which allow them to
have direct signaling.
A)
B)
C)
D)
E)
Desmosomes
Gap junctions
Intermediate filaments
Hemidesmosomes
Tight junctions
Apoptosis
• Programmed cell death
• Cell shrinks and forms rounder shape
– Due to destruction of nucleus and cytoskeleton
• Plasma membrane forms blebs
– Irregular extensions that break away
Kerr, Wyllie, and Currie found that hormone signals can initiate
apoptosis
• ACTH known to increase number of adrenal cortex cells
• Prednisolone suppresses ACTH synthesis and decrease
number of adrenal cortex cells
• Even in control samples, researchers observed apoptosis
• In prednisolone-treated rats, the rate was higher
• Results indicate tissues decrease cell number and that cell
death was induced, in this case, by a hormone
• Coined term apoptosis