Cell communication and cell cycle Cell communication and cell cycle

Lecture 5
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Why do cells need to communicate?
Growth
Cell division
Differentiation
Movement
Metabolism
Secretion
Cell death (apoptosis)
Biologists have discovered some universal mechanisms of
cellular regulation
Chapters 11 and 12
Cells use chemical signals for communication
Talking cell or
transmitting cell
Listening cell or
target cell
Chemical
signals
How do cells communicate? How do cells communicate?
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Signaling transduction pathway
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How do cells communicate? How do cells communicate?
Local signaling (paracrine and synaptic signaling)
Two types of signaling pathways Two types of signaling pathways
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Long distance signaling (hormonal
or endocrine signaling)
Two types of signaling pathways Two types of signaling pathways
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The Three Stages of Cell Signaling The Three Stages of Cell Signaling
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Membrane associated receptors involved in cell signaling
G protein-coupled receptors
tyrosine kinases receptors
Ion channel receptors
Intracellular receptors
G protein-coupled receptor G protein-coupled receptor
G-protein-coupled receptor
(GPCRs) are the largest family of
cell-surface receptors
A GPCR is a plasma membrane
receptor that works with the help of
a G protein
The G protein acts as an on/off
switch: If GDP is bound to the G
protein, the G protein is inactive
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Found in the cytosol or
nucleus of target cells
Small or hydrophobic
chemical messengers can
readily cross the membrane
and activate receptors
Examples of hydrophobic
messengers are the steroid
and thyroid hormones of
animals
An activated hormone-
receptor complex can act as
a transcription factor, turning
on specific genes
Intracellular receptors Intracellular receptors
Relay of the signal from receptor molecule through a
cascade of molecular interactions to the target
molecules in the cell.
Involves multiple steps
Signal amplification
Coordination and regulation of cellular response
The relay of information is carried by interactions
between different proteins which together constitute
a signaling pathway.
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Transduction Transduction
Protein Kinases: transfer phosphate group from
ATP to the substrate protein
Phosphatases: Remove phosphate from
phosphorylated proteins
Protein kinase
Phosphatase
P
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Protein kinases and phosphatases: major relay molecules Protein kinases and phosphatases: major relay molecules
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Phosphorylation acting as a signal Phosphorylation acting as a signal
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Second messengers Second messengers
The extracellular signal molecule (ligand) that
binds to the receptor is a pathways first
messenger
Second messengers are small, nonprotein, water-
soluble molecules or ions that spread throughout a
cell by diffusion
Second messengers participate in pathways
initiated by GPCRs and RTKs
Cyclic AMP and calcium ions are common second
messengers
Second messengers Second messengers
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Ca
+2
as second messenger Ca
+2
as second messenger
Nuclear and Cytoplasmic Responses Nuclear and Cytoplasmic Responses
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Ultimately, a signal
transduction pathway leads
to regulation of one or more
cellular activities
The response may occur in
the cytoplasm or in the
nucleus
Many signaling pathways
regulate the synthesis of
enzymes or other proteins,
usually by turning genes on
or off in the nucleus
The final activated molecule
in the signaling pathway
may function as a
transcription factor
Cytoplasmic Responses Cytoplasmic Responses
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Cytoplasmic response to a
signal: the stimulation of
glycogen breakdown by
epinephrine.
Cell Cycle Cell Cycle
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Cellular Organization of the Genetic Material
A genome can consist of
a single DNA molecule
(common in prokaryotic
cells) or a number of DNA
molecules (common in
eukaryotic cells)
Somatic cells
(nonreproductive cells) have
two sets of chromosomes
Gametes (reproductive
cells: sperm and eggs) have
half as many chromosomes
as somatic cells
Distribution of Chromosomes During Eukaryotic Cell Division Distribution of Chromosomes During Eukaryotic Cell Division
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Mitosis Meiosis
Division of somatic
cells
Two daughter cells are
produced with same
amount of DNA as
mother cell
Division of gamete
cells (Sperm and
ovum)
Four daughter cells
are produced with
half the amount DNA
as mother cell
Cell Cycle Cell Cycle
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Interphase
Mitotic phase
Constitutes 90% of cell cycle
and can be divided into three
sub phases:
1. G1 phase (first gap)
2. S phase (DNA synthesis
phase)
3. G2 phase (second gap)
Constitutes only 10% cell cycle
and can be divided into six sub
phases:
1. Prophase
2. Prometaphase
3. Metaphase
4. Anaphase
5. Telophase
6. Cytokinesis
Mitotic cell cycle Mitotic cell cycle
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Prophase
Chromatins condense into
discrete chromosomes
Centrosomes move apart
Nucleoli disappear
Mitotic spindle begins to
form
Mitosis Mitosis
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Prometaphase
Nuclear membrane fragments
Microtubules grow
Each of the two chromatids
have kinetochore proteins at
centromere
Some microtubules attach to
kinetochores called
kinetochore microtubules
Mitosis Mitosis
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Metaphase
Mitosis Mitosis
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All the chromosomes assemble at
metaphase plate
For each chromosome sister
chromatids are attached to
kinetochore microtubules arising
from opposite poles
Anaphase
Sister chromatids
separate due to cleavage
of cohesin protein
Each chromatid now
behaves as a
chromosome
Daughter chromosomes
move towards opposite
poles due to shortening of
kinetochore microtubules
Mitosis Mitosis
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Telophase
Two daughter nuclei form
in the cell
Nuclear envelope
reappears
Spindle microtubules
depolymerize
Chromosomes become
less condensed
Karyokinesis (division of
nucleus) completes
Mitosis Mitosis
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Cytokinesis
Formation of cell furrow
Division of cytoplasm to give rise to
two daughter cells
Mitosis Mitosis
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Checkpoints are essential for the correct distribution of complete
chromosome sets between daughter cells
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Parent DNA strands are intact
before DNA replication begins
Chromosomes are
aligned properly at the
metaphase plate
before Anaphase
Newly synthesized DNA
strands are complete and
intact before Mitosis
Checkpoints Checkpoints
G
1
checkpoint
G
1
G
1
G
0
(a) Cell receives a go-ahead
signal.
(b) Cell does not receive a
go-ahead signal.
For many cells G1 checkpoint is the most important checkpoints For many cells G1 checkpoint is the most important checkpoints
Family of Cyclins and Cyclin Dependent Kinases
(Cdks) are major proteins involved in regulation
of cell cycle
They serve as internal signals of the cell
Cdks are expressed throughout the cell cycle
however activated only after binding with
cyclins which are synthesized during S phase
and accumulate through G2 phase
Cyclins get degraded after metaphase and cell
enters the G1 phase
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Major cell cycle regulating protein (Internal signals) Major cell cycle regulating protein (Internal signals)
Cdk
G1
S
G2
M
Cyclin
3. Cyclin-Cdk complex
formation
1. Synthesis of cyclin
2. Accumulation
of cyclin
5. Degradation of
cyclin
4. Entry in
mitosis
6. Entry in G1
phase
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Regulation of cell cycle by Cyclins and cyclin dependent kinases Regulation of cell cycle by Cyclins and cyclin dependent kinases
In addition to internal signals following external
signals are also required for the progression of cell
cycle
Nutrients
Growth factors
Space (Crowded cells stop dividing) also known as
density dependent inhibition
Substratum for anchorage (anchorage
dependence)
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Regulation of cell cycle by external signals Regulation of cell cycle by external signals
Cancer cells do not stop at cell cycle
checkpoints
Continue to divide even after the presence of
errors in the DNA
Do not exhibit density dependent inhibition
(form multiple layers of cells)
Do not require anchorage with the substratum
Normal mammalian cells
Cancer cells
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Cancer cells lose dependence on internal and external signals for
proliferation
Cancer cells lose dependence on internal and external signals for
proliferation
Essential for the generation of gametes
(eggs and sperms)
The daughter cells formed at the end of
meiosis are haploid (single set of
chromosomes)
When the gametes fuse during
fertilization a zygote is formed which has
two sets of the chromosomes one set
from each parent
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Meiosis or reductional cell division Meiosis or reductional cell division
Duplication of homologous
chromosomes
Meiosis I
Separation of homologous
chromosomes
Diploid cell
Diploid cell with
duplicated
chromosomes
Haploid cells with
duplicated chromosomes
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Meiosis reduces chromosome number Meiosis reduces chromosome number
Meiosis II
Separation of
sister chromatids
(Similar to
mitosis)
Haploid cells with unduplicated chromosomes
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Meiosis reduces chromosome number cntd Meiosis reduces chromosome number cntd