Chapter 11: Cell Communication.
Why do cells need to signal?
• Cells communicate with each other through
cell-cell signaling.
• Signaling molecules are the chemical
messengers used (sometimes called ligands)
Signal transduction pathways
•Are similar in microbes and mammals, suggesting an early
origin
–Suggests an evolutionary connection.
1 Exchange of
mating factors.
Each cell type
secretes a
mating factor
that binds to
receptors on
the other cell
type.
2 Mating. Binding
of the factors to
receptors
induces changes
in the cells that
lead to their
fusion.
! factor
Receptor
a
!
Yeast cell, a factor Yeast cell,
mating type !
mating type a
a
!
3 New a/! cell.
Figure 11.2
The nucleus of
the fused cell
includes all the
genes from the
a and a cells.
a/!
Signaling in multicellular organisms
• Can be both Local or Long-Distance
• Local Signaling
– Paracrine: The signaling molecule is released and diffuses
to the neighboring cells. This is local Signaling.
– Synaptic Signaling. Nerve cells signal across a synapse.
Long Distance Signaling
•Endocrine: Signal is released into a carrier system, such as blood,
which carries the molecules to the target cells, which can be far away.
– Examples of this are hormones.
Long-distance signaling
Endocrine cell
Blood
vessel
Local signaling
Target cell
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across
synapse
Secretory
vesicle
Local regulator
diffuses through
extracellular fluid
Figure 11.5 A B
(a) Paracrine signaling. A secreting cell acts
on nearby target cells by discharging
molecules of a local regulator (a growth
factor, for example) into the extracellular
fluid.
Hormone travels
in bloodstream
to target cells
Target
cell
Target cell
is stimulated
(b) Synaptic signaling. A nerve cell
releases neurotransmitter molecules
into a synapse, stimulating the
target cell.
Figure 11.5
(c) Hormonal signaling. Specialized
endocrine cells secrete hormones
into body fluids, often the blood.
Hormones may reach virtually all
C body cells.
The signal-transduction pathway
• For most signals the signaling molecule does not
enter the cell
•
– The signal is relayed through the membrane, from the
outside to the inside.
•
– Reception
– Transduction
– Response
• How is this done?
•
EXTRACELLULAR
FLUID
The signaling molecule (ligand) binds to a
membrane receptor on the outside of the cell.
•
This receptor spans the membrane and has both
an extracellular and a cytosolic domain.
•
The cytosolic domain changes shape when
bound to ligand.
The response of the cell to a signaling molecule is mediated
through a signal-transduction pathway.
This occurs through 3 steps.
1 Reception
Plasma membrane
CYTOPLASM
2 Transduction
3 Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
– The ligand is not always a diffusible molecule
Signal
molecule
Figure 11.6
G-Protein linked receptors
Receptors
• There are three major types of membrane
receptors.
– G-Protein linked receptors. Figure 11.7a
– Tyrosine-Kinase Receptors
– Ligand-gated Ion channels.
Focus on the G-Protein linked receptors
Know the other pathways!
•
•
•
Are connected to a G-protein that is activated when a ligand binds to
the receptor.
The activation triggers the displacement of the GDP by GTP. This
activated G-protein then goes on to activate other proteins.
Example: Slime mold cAMP receptor system.
Tyrosine-Kinase Receptors.
•
•
•
•
Ligand-gated Ion channels
Form dimers.
Phosphorylate the tyrosine amino acids on the other receptor
This activates the receptor dimer
Example: Growth factor receptor.
Signal
Signal-binding sitea
molecule
!Helix in the
Membrane
Tyr
Tyr
Tyr
Tyrosines
Signal
molecule
•
Binding of ligand opens up an ion channel.
•
The opening of the channel leads to a net flow of
ions into or out of the cell.
Gate
closed
Ligand-gated
ion channel receptor
Ions
Plasma
Membrane
Gate open
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Tyr
Receptor tyrosine
kinase proteins
(inactive monomers)
CYTOPLASM
Signal
molecule
(ligand)
Tyr
Tyr
Tyr
•
This triggers an intracellular response. Na+, Ca2+
Dimer
Cellular
response
Activated
relay proteins
Tyr
Tyr
Tyr
Figure 11.7
Tyr
Tyr
Tyr
6
ATP
Activated tyrosinekinase regions
(unphosphorylated
dimer)
6 ADP
P Tyr
P Tyr
P Tyr
P Tyr
P Tyr
P Tyr
Tyr P
Tyr P
Tyr P
Fully activated receptor
tyrosine-kinase
(phosphorylated
dimer)
Tyr P
Tyr P
Tyr P
Cellular
response 1
Cellular
response 2
Gate close
Inactive
relay proteins
Figure 11.7
Intracellular Receptors.
•
•
Small non polar molecules, Hormones, can travel through the
membrane where they can bind to an internal receptor protein
Usually activates a transcription factor.
Hormone
EXTRACELLULAR
(testosterone) FLUID
1 The steroid
hormone testosterone
passes through the
plasma membrane.
Plasma
membrane
Receptor
protein
Hormonereceptor
complex
Transduction
The signal is relayed via cascades of molecular interactions in the cell.
•
•
•
•
Amplification of the signal can be achieved by phosphorylation cascades
and second messengers
Adding or removing phosphate groups regulates protein activity.
Kinases use ATP to phosphorylate molecules.
Phosphatases remove phosphate groups from molecules.
Signal molecule
2 Testosterone binds
to a receptor protein
in the cytoplasm,
activating it.
e
Figure 11.9
ad
5 The mRNA is
translated into a
specific protein.
sc
CYTOPLASM
New protein
ca
stimulates the
transcription of
the gene into mRNA.
io n
NUCLEUS
la t
4 The bound protein
PP
o ry
mRNA
Active P
protein
kinase
2
Inactive
protein kinaseATP
Active P
ADP
3
protein
kinase
Pi PP
3
Inactive
protein ATP ADP
P
Active
protein
P i PP
Pi
ph
Figure 11.6
receptor complex
enters the nucleus
and binds to specific
genes.
os
Active
protein
kinase
1
Inactive
protein kinaseATP
ADP
2
Ph
Inactive
protein kinase
1
3 The hormone-
DNA
Activated relay
molecule
Receptor
Cellular
response
Second messengers
Nuclear response to a signal
Ca2+
Regulate genes by activating transcription
factors that turn genes on or off
– cAMP and
or other small molecules (IP3, DAG)
1 A signal molecule binds
2 Phospholipase C cleaves a
to a receptor, leading to
plasma membrane phospholipid
activation of phospholipase C. called PIP2 into DAG and IP3.
EXTRACELLULAR
FLUID
3 DAG functions as
a second messenger
in other pathways.
Growth factor
Signal molecule
(first messenger)
Reception
Receptor
G protein
DAG
Phosphorylation
cascade
GTP
Figure 11.13
G-protein-linked
receptor
Phospholipase C
PIP2
Transduction
IP3
(second messenger)
CYTOPLASM
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Various
proteins
activated
Ca2+
Ca2+
Inactive
transcription Active
factor
transcription
factor
P
Cellular
response
DNA
(second
messenger)
4 IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open.
5 Calcium ions flow out of
the ER (down their concentration gradient), raising
the Ca2+ level in the cytosol.
Gene
6 The calcium ions
activate the next
protein in one or more
signaling pathways.
Figure 11.14
The signaling is very specific
• The same signaling molecule can lead to
different responses in different types of
cells.
Signal
molecule
EXTRACELLULAR
FLUID
G protein
DAG
Relay
molecules
GTP
Response Response
2
G-protein-linked
receptor
Phospholipase C
PIP2
IP3
(second messenger)
3
IP3-gated
calcium channel
Endoplasmic
reticulum (ER)
Activation
or inhibition
Response 4
Figure 11.17
Signal molecule
(first messenger)
Receptor
Response 1
mRNA
NUCLEUS
Signal Transduction
• Receptors only bind to a specific ligand.
– Example: Epinephrine
– In liver it triggers breakdown of glycogen
– In the heart it increase the heart beat.
Response
Ca2+
Ca2+
(second
messenger)
Response 5
Various
proteins
activated
Cellular
response
Summary of signaling.
• Via membrane proteins.
– G-Protein linked receptors. Many different G-proteins
– Tyrosine-Kinase Receptors.
– Ligand-gated Ion channels.
• Directly Intracellular Receptors
– Non-polar molecules that bind to receptors inside cells. Usually
activate transcription factors.
• Both can lead to amplification of signal.
– Branching: Binding of signaling molecule can trigger several
different responses inside cell.
– Combination of two different signals.
Chapter 12 The Cell Cycle.
Every living organism must be able to reproduce in
order to survive.
• Reproduction occurs by Cell Division.
– It is part of the Cell Cycle.
– It results in genetically identical daughter cells
• The Cell Cycle is the foundation of life.
• Unicellular organisms
– Reproduce by cell division
• Multicellular organisms depend on cell division for
– Development from a fertilized cell
– Growth
– Repair
Genome
Brief review
• Eukaryotic cell division consists of
– Mitosis, the division of the nucleus
– Cytokinesis, the division of the cytoplasm
• In meiosis
– Sex cells are produced after a reduction in
chromosome number
• The cells genetic information is called its genome.
• The genome contains the recipe for running and building
the cell.
• The genome contains all the chromosomes.
• The chromosome is made up of a very long linear DNA
strand containing up to thousands of genes, each gene
specifying a specific protein.
• This strand is associated with various proteins that
maintain the structure and control the activity of genes.
• This DNA protein complex is called chromatin.
– A cell can have 3 m long DNA strands even though it is only 10 !m
long.
The Cell Cycle is divided into Two Phases
Interphase and Mitosis (Mitotic phase)
•
•
•
•
•
•
Interphase is split into 3 phases
G1, S, G2
After G2 the cell enters mitosis.
•
DNA is Duplicated in S phase! Not in mitosis.
After the S phase each chromosome has an identical copy, the pair are
called sister chromatids.
They are joined at the Centeromere, a waist like region near the center
of the chromosome.
Kinetochores, where the microtubules attach, are formed here as well.
INTERPHASE
S
(DNA synthesis)
Chromosome
duplication
(including DNA
synthesis)
Once duplicated, a chromosome
consists of two sister chromatids
connected at the centromere. Each
chromatid contains a copy of the
DNA molecule.
Centromere
C
M y to
ito k i
si n e
s si
s
G1
0.5 !m
A eukaryotic cell has multiple
chromosomes, one of which is
represented here. Before
duplication, each chromosome
has a single DNA molecule.
G2
MI
(M TOT
) P IC
HA
SE
Figure 12.5
Separation
of sister
chromatids
Mechanical processes separate
the sister chromatids into two
chromosomes and distribute
them to two daughter cells.
Figure 12.4
Sister
chromatids
Centromeres
Sister chromatids
Mitosis is split into five subphases
It is made up of mitosis and cytokinesis
•
Prophase
– Two centerosomes already formed begin to move towards opposite poles of
the cell. Microtubules grow from the centerosomes. Chromosomes begin to
condense and sister chromatid pairs become visible.
•
Prometaphase
– Nuclear envelope begins to break down.
– Each of the two sister chromatids has now a structure called Kinetochore
located at the centeromer region. Microtubules begin to attach to the
kinetochores.
•
G2 OF
PROMETAPHASE
PROPHASE
INTERPHASE
Centrosomes
Aster
Fragments
Early mitotic
Kinetochore
(with centriole pairs) Chromatin
of
nuclear
Centromere
(duplicated) spindle
Nonkinetochore
envelope
microtubules
Figure 12.6
Nucleolus Nuclear Plasma
envelopemembrane
Chromosome, consisting
of two sister chromatids
Kinetochore
microtubule
Metaphase
– Centerosomes are at opposite poles. Chromosomes convene in the center
between the two centerosomes .
•
METAPHASE
Anaphase
– The two sister chromatids are separated as the microtubules shorten.
•
ANAPHASE
Metaphase
plate
TELOPHASE AND CYTOKINESIS
Cleavage
furrow
Telophase
– Two daughter nuclei form and the nuclear envelope arises from the fragments
of the parents nuclear envelope. The chromosomes become less tightly
coiled.
Figure 12.6
Spindle
Centrosome at Daughter
one spindle polechromosomes
Nuclear
envelope
forming
Nucleolus
forming
Animal Mitosis (Bio Flix)
• Every Eukaryotic cell has a characteristic number of
chromosomes.
– Diploid cells have pairs of homologous chromosomes.
– Haploid cells have single chromosomes. The only haploid
cells in humans are the gametes.
Plant and animal Cytokinesis
•
Bacteria divide by binary fission
Cytokinesis, the division of the cytoplasm usually finishes at
the end of telophase.
•In animal cells
•
–Cytokinesis occurs by a process
known as cleavage, forming a
cleavage furrow
In plant cells, during
cytokinesis
– A cell plate forms
Origin of
replication
E. coli cell
Chromosome replication
1 begins.
Soon thereafter, one copy of
the origin moves rapidly toward
the other end of the cell.
2 Replication continues. One copy of
the origin is now at each end of
the cell.
Cleavage furrow
100 !m
Vesicles
forming
cell plate
Wall of
1 !m
patent cell Cell plateNew cell wall
3 Replication finishes. The plasma
membrane grows inward, and
new cell wall is deposited.
Figure 12.11 4 Two daughter cells result.
Contractile ring of
microfilaments
Figure 12.9 A
Daughter cells
(a) Cleavage of an animal cell (SEM)
Daughter cells
(b) Cell plate formation in a plant cell (SEM)
Figure 12.9 B
Cell wall
Two copies
of origin
Origin
Plasma
Membrane
Bacterial
Chromosome
Origin
How many chromatids does a human cell
have after undergoing S-phase?
Can the repeated cycle of cell divisions
continue unchecked?
A) 46
B) 19
C) 23
D) 32
E) 92
Cell check points
• The cell cycle is regulated by a molecular control
system
• There are 3 major checkpoints during the cell cycle.
(a) Fluctuation of MPF activity and
cyclin concentration during
the cell cycle
M
G1 S G2 M
G1 S G2 M
MPF activity
Cyclin
Time
(b) Molecular mechanisms that
help regulate the cell cycle
1 Synthesis of cyclin begins in late S
phase and continues through G2.
Because cyclin is protected from
degradation during this stage, it
accumulates.
G1 checkpoint
M
Figure 12.14
G2
Cdk
Cyclin is
degraded
M checkpoint
G2 checkpoint
4 During anaphase, the cyclin component
Figure 12.17 A, B
of MPF is degraded, terminating the M
phase. The cell enters the G1 phase.
2
Degraded
Cyclin
M
G1
G
S
the cell favor degradation
of cyclin, and the Cdk
component of MPF is
recycled.
S
Control
system
1
5 During G1, conditions in
G
•
– The G1 checkpoint goes into S or into G0
– The G2 checkpoint
– And the Mitotic checkpoint.
Why are checkpoints necessary?
Cell cycle clock
– Cyclins proteins whose concentrations cycles during the cell cycle
– Cyclin-dependent-Kinases (CDK’s) that are activated when bound to the
cyclins.
– MPF maturation (mitotic) promotion factor at the G2 checkpoint, a cdkcyclin complex.
G2
Cdk
checkpoint
MPF
Cyclin
2 Accumulated cyclin molecules
combine with recycled Cdk molecules, producing enough molecules
of MPF to pass the G2 checkpoint and
initiate the events of mitosis.
3 MPF promotes mitosis by phosphorylating
various proteins. MPF‘s activity peaks during
metaphase.
•
•
•
Growth factors
PDGF ( Platelet derived growth factor) for fibroblasts affect the
G1 checkpoint.
Density dependence and anchorage dependence inhibition.
•
Growth factors
– PDGF ( Platelet derived growth factor) for fibroblasts affect the G1
checkpoint.
•
– Can lower density of growth factors.
– There is also contact inhibition.
(a) Normal mammalian cells. The
availability of nutrients, growth
factors, and a substratum for
attachment limits cell
density to a single layer.
Control of Cell growth
Density dependence and anchorage dependence inhibition.
– Can lower density of growth factors.
– There is also contact inhibition.
Cells anchor to dish surface and
divide (anchorage dependence).
When cells have formed a complete single layer, they
stop dividing
(density-dependent inhibition).
(a) Normal mammalian cells. The
availability of nutrients, growth
factors, and a substratum for
attachment limits cell
density to a single layer.
If some cells are scraped away, the remaining cells
divide to fill the gap and then stop (density-dependent
inhibition).
Figure 12.18 A
Cancer
•
Cancer cells
–
–
–
–
–
Exhibit neither density-dependent inhibition nor anchorage dependence
Have escaped from cell cycle control
Make excessive amounts of GF
Have lost the ability to be controlled by GF.
GF signaling pathway abnormal.
Lymph
vessel
Tumor
Glandular
tissue
Figure 12.20
Blood
vessel
Cancer cell
Metastatic
Tumor
When cells have formed a complete single layer, they
stop dividing
(density-dependent inhibition).
If some cells are scraped away, the remaining cells
divide to fill the gap and then stop (density-dependent
inhibition).
Figure 12.19 A
25 !m
Cells anchor to dish surface and
divide (anchorage dependence).
25 !m