cell_communication

AP Biology Rapid Learning Series - 06
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Cell CommunicationCell Communication
and Cycle
AP Biology Rapid Learning Series
www.RapidLearningCenter.com/
© Rapid Learning Inc. All rights reserved.
AP Biology Rapid Learning Series
Wayne Huang, PhD
Andrew Graham, PhD
Elizabeth James, PhD
Casandra Rauser, PhD
Jessica Habashi, PhD
Sara Olson, PhD
Jessica Barnes, PhD

Learning Objectives
By completing this tutorial, you will learn about:
Cell communication
Chemical signaling
Signal transduction
Signal amplification
Cell cycle
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Concept Map – The Cell
Cell
Communication
Cell proliferationCell proliferation
CDK/cyclin
Cell
PGCRs
Cancer RTKs
Broken control Cell signals
Signal
transduction
IntracellularIntracellular
Receptors
pp
Gene activationGene activation
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transductiontransduction
amplification
Signal
amplification
messenger
Secondary
messenger
CDK: Cyclin-dependent kinases
RTK: receptor tyrosine kinase
PGCR: protein G cell receptors

Concept Map – Cell Communication
Environment
change Sensing
Biochemical
Reactions
Signal initiationSignal initiation
Chemical signals
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Cell communicationCell communication
Coordinated
cell function
Coordinated
cell function
Reaction Body defense
Feedback
Cell
Communication
Cell:Cell interfaces and junctions.
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Signaling between cells.
Cell signal receptors.
Significance of G protein.

Cell:Cell Contact
Cell to cell contacts are vital
in multicellular organisms.
There are 4 kinds of cell
junction in vertebrate cells.
1. Tight junctions
2. Adherens junctions
3. Gap junction
4. Desmosomes
Plant cells have
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Plant cells have
plasmodesmata as a junction
between their cells. They are
microscopic channels
facilitating transport and
cell:cell communication.
Tight Junction
Tight junctions seal
adjacent epithelial cells
in a narrow band just
beneath their surface.
The functions of tight
junctions include:
1. Block the movement of
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integral membrane
proteins between the two
surfaces of the cell.
2. Prevent the passage of
molecules and ions
through the space
between cells.

Adherens Junctions
Adheren junctions consist of
cadherens and catenins and provide
strong mechanical attachments.
Cadherins are a
transmembrane
protein that forms
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homodimers. β-
catenin and α-catenin
form a complex with
the intracellular
portion of the
cadherin molecule.
Gap Junctions
Gap junctions are junctions
between certain animal cells types.
They allow different molecules and
ions (usually intracellular
signaling moleculesO to pass
One gap junction
is made up of two
connexons that
connect acrossg g p
between cells. the intercellular
space. These are
similar to
plasmodesmata
that join plant
cells.
10/45
Gap junctions are in
almost all cells,
except mobile cells.
They are important in
cardiac cells to pass
information to
contract the heart.

Desmosome Junctions
Desmosomes are localized patches
that hold two cells together very
tightly. They are attached to
intermediate filament in skin cells.
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Desmosomes belong to the cadherin family of
adhesion molecules. They attach the cell
surface protein to the cell’s cytoskeleton.
They are transmembrane proteins that form a
bridge between adjacent epithelial cells.
Paracrine Signaling
Paracrine signaling is
between close cells.
The chemical signal is
called the paracrine agent.p g
Both paracrine and autocrine
signaling is between cells that
l B t i
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are close. But paracrine
signaling affects cells of a
different type than the cell
doing the signal secretion.
Autocrine signaling affects
cells of the same type.

Endocrine Signaling
1 Pineal gland
Major endocrine glands.In endocrine signaling: signal
molecules, hormones, are
released into the blood stream
and act on target cells distributed
th h t th b d 1. Pineal gland
2. Pituitary gland
3. Thyroid gland
4. Thymus
5. Adrenal gland
6. Pancreas
7. Ovary
8. Testis
throughout the body.
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The endocrine signal is a distant signal
Target cells have receptors that bind the
hormones. Endocrine signaling acts at a
distance. The target cell is distant from the
cell that makes the signal (hormone).
Signal Reception
1. A signal is bound by a
receptor.
2 Receptors are specific for2. Receptors are specific for
their target signal, like a
lock and key fit.
3. The receptor is a protein
on the cell membrane or in
the cytoplasm or cell
nucleus that binds a
specific molecule (called
Transmembrane Receptor
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the ligand).
4. Ligands change the
behavior of receptor
proteins resulting in
physiological changes. E=extracellular space;
I=intracellular space;
P=plasma membrane

Receptor Types
There are 3 classes of receptors.
1. Receptors tyrosine kinases (RTK).
2. G-protein coupled receptors, (GPCR).
3. Intracellular receptors.
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Receptor Tyrosine Kinase
Characteristics:
RTK is a transmembrane protein having kinase enzyme
activities.
An extracellular ligand binding domainAn extracellular ligand binding domain.
An intracellular tyrosine kinase domain.
An intracellular regulatory domain.
The transmembrane domain ligand binding activates the
kinase via phosphorylation and dimerization.
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Ligand
binding
Phosphate group
Ligand

7 Classes of RTK
Class III
PDGF
Class IV
FGF receptors
Class V
Vascular
Class II
Insulin receptor,
IGF-1 receptor
receptors, c-Kit endothelial cell
growth factor
(VEGF) receptor
Class VI
Hepatocyte growth
factor (HGF) and
scatter factor (SC)
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Class I
EGF receptor,
NEU/HER2,
HER3
scatter factor (SC)
receptors
Class VII
Neurotrophin receptor
family (trkA, trkB, trkC)
and NGF receptor.
G-Protein-Coupled Receptor
A receptor containing 7 Transmembrane Domains
The receptor has a cellular domain that binds to G proteins
Ligand binding site
Outside of cell
Cell membrane
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Cytoplasm side
G protein

3 Kinds of G Protein Receptors
Adenylate cyclase activator
GPCRs: Increase cAMP
concentration
PLC-g GPCRs: Increase
diacylglycerol (DAG) and
inositoltrisphosphate
(IP3)concentration. (IP3).
Photoreceptors:
cAMP, DAG,
IP3 and
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Photoreceptors:
Transduction:
Decrease cGMP
concentration.
IP3 and
cGMP are all
second
messengers.
GPCR Signal Transduction
1) A signal molecule binds to a
4 Steps of GPCR signal transduction
signal
Receptor
1) A signal molecule binds to a
receptor --> conformation
change
2) G protein activation: An inactive
G-(GDP)-protein now binds GTP
(replacing GDP)
3) G-Protein has its GTP
hydrolyzed --> inactivates G-
protein membrane
membrane
GDP-G protein
(inactive)
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4) Meanwhile GTP hydrolysis
activates other inactive
enzymes. GTP-G protein
(active)
Target
(inactive)
Target
(active)

Intracellular Hormone Receptors
Hormone receptors are proteins
within the cytoplasm, therefore
they do not require all of the
Plasma membrane
Nucleus
they do not require all of the
above signal transduction
pathways
Hormones pass membrane freely
These receptors have double
functions.
They are capable of binding
Gene
expression
DNA
21/45
They are capable of binding
hormone
Upon binding, they translocate to
nucleus and directly activate
gene transcription.
Hormone receptor
Hormone
Signal Transduction
Signal transduction pathway.
Ki d h h t
22/45
Kinases and phosphatases.
Signal amplification.
Second messenger.
Cyclic AMP

Signal Transduction Pathway
Many types of signals, all share same transduction
mechanism
RECEPTION -->TRANSDUCTION --> RESPONSE
Signal
Receptor
Reception
Cell membrane
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Transduction
Transducer
Response
Effector
Kinase and Phosphatase
Phosphorylation and dephosphorylation of proteins is an
important signal transduction mechanism.
Kinase:Kinase:
Protein + ATP Protein-Pi (phospho-protein) + ADP
Phosphatase:
Protein-Pi Protein (un-phosphorylated)
Kinase
Phosphatase
24/45
Phosphotase
Kinase

Protein Kinase
A protein kinase is an enzyme that modifies other
proteins by adding phosphate groups to them.
The addition of a phosphate group (phosphorylation)
typically causes a functional change in the target protein.
Protein Kinase
Serine:threonine specific
protein kinases.
Tyrosine specific
protein kinases.
25/45
Phosphorylate the OH group of
serine or threonine.
Protein kinase activity is regulated
by events such as DNA damage and
other chemical signals e.g.
cAMP/cGMP, diacylglycerol and
Ca2+/calmodulin
Phosphorylate tyrosine
amino acid residues. They
act as growth factor
receptors in downstream
signaling events from growth
factors.
Phosphatase
A phosphatase is an enzyme that removes the phosphate
group from its substrate by hydrolyzing phosphoric acid
monoesters into phosphate ion and a free hydroxyl group.
26/45
Two main phosphatase categories: Cysteine dependent
phosphatases (CDPs) and Metallo phosphatases (which
require metal ions in the active site to function).

Kinase VS. Phosphatase Function
What are the major
differences between a
kinase and phosphatase
functions?
Kinases are primarily
involved in cell
proliferation and
oncogenesis.g
Phosphatases inhibit cell
27/45
proliferation and act in
anti-oncogenesis.
Signal Amplification
Cell signal can be amplified through signal transduction.
Th f t d t i thThree factors determine the
strength of an amplified signal.
1. The lifetime of the hormone
receptor complex.
2. The amount and lifetime of the
receptor-effector protein
complex.
3. Deactivation of the activated
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receptor.

Ras Signal Amplification
Receptor
Growth factorGrowth factor
1 molecule of growth factor
Receptor
1 Ras-raf
nx Mek
1 molecule of ras-raf
phosphorylates n x
Mek molecules
n molecule of Mek
phosphorylates n x m
2 molecules of Receptor
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n x m MAPK
MAPK molecules
Transcription (effector)Transcription (effector)
The signal is amplified n x m fold
TGF Ligand Signaling
Intercellular signaling pathway involved in TGF-beta
ligand signaling.
1 SMAD pathway is a signaling pathway1. SMAD pathway is a signaling pathway
that TGF (growth factor) uses.
2. TGFs binds to a type II receptor which
recruits and phosphorylates a type I
receptor.
3. The type I receptor recruits and
phosphorylates a receptor regulated
SMAD. (SMADs are a class of proteins
that modulate the activity of transforming
30/45
y g
growth factor ligands.)
4. The R-SMAD then binds to SMAD which
leads to activation of mitogen activated
protein kinase.
5. Apoptosis (cell death) is triggered by this
activation.

Secondary Messenger
Secondary messengers are molecules that relay signals received from
cell surface receptors to target molecules in the cytosol or nucleus.
Second messengersSecond messengers
amplify the strength of a
signal.
3 Classes of second
messengers:
1. Cyclic nucleotides
(cAMP, cGMP)
2. Inositol triphosphate
(IP3), diacylglycerol
(DAG).
3. Calcium ions (Ca2+).
2nd Messenger
nucleus
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cAMP
cAMP is synthesized from ATP
by adenylyl cyclase
Hormone/receptor --> adenylyl
cyclase --> cAMP --> CREB -->
gene expression
Adenylyl
cyclase
gene expression
Or: ligand/receptor --> adenylyl
cyclase --> cAMP --> PKA -->
phosphorylate other proteins
ATP
cAMP
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IP3 and DAG -- Phospholipase
■ Phospolipase
Phospholipases and phospholipids are an important part of
signal transduction.
■ IP3 and DAG are made from PIP2 which is a
membrane lipid
■ Phospholipase C-γ: interacts with RTK. Increase IP3 -->
increase Calcium ions -- > increase PKC activity
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Phospholipase C-γ
PIP2 IP3 (inositol 1,4,5-phosphate
+
Diacylglycerol (DAG)
IP3 and DAG Signal
DAG
PKC activation
IP3 --> Ca2+
Protein
hormones
Neutrontransmitter
GABA
GPCR PLC-γ
34/45

Role of Calcium Influx in Cells
Ca2+ entering a cell can have these
effects:
1. Muscle contraction
2. Exocytosis e.g. release of2. Exocytosis e.g. release of
neurotransmitters.
3. Secretion of hormones.
4. Activation of T and B cells.
5. Adhesion of cells to the extracellular
matrix (ECM).
6. Apoptosis.
7. Activation of protein kinase C (PKC).
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Calcium ions: In and Out
There are various mechanisms for Ca2+ signaling.
Voltage-gated channels
open in response to an
action potential;
Receptor-operated channels
e g Neurotransmitter effect on post synaptic membrane
p ;
found in muscle and
nerve cells:
allow quick influx of ions
in large amounts.
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G-protein-coupled receptors
(GPCRs)
GPCR --> PLC --> IP3 --> Ca2+
e.g. Neurotransmitter effect on post-synaptic membrane.

Cell Cycle
Cell division.
37/45
Tumors growth and suppression.
Cell Cycle – Four Phases
■ A cell cycle is a cell
proliferation cycle from one
cell to two cells.
S
■ It consists of four phases:
G1 – first growth phase
S -- DNA synthesis
G2 – second growth phase
M -- mitosis
■ G0 phase is resting quiescent
G1
S
2N >2N
4N
4N
2N
2N
G2
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cells which are not dividing. M
4N

Cyclins Cell Cycle Control
Cyclins belong to a family of proteins that are involved in
control of the cell cycle.
Cyclins fluctuate in
concentration, depending on
the phase of cell cycle.
Cyclins regulate the cycle by
bi di t d ti ti
39/45
binding to and activating a
kinase.
Different phases are controlled
by different cyclins and Cyclin-
dependent kinases (CDKs).
Cell Cycle Schematic:
outer ring: I=Interphase,
M=Metaphase;
inner ring: M=Mitosis.
Cell Cycle Checkpoint
Four major checkpoints:
G checkpoints: Cells arrest in G
Cell cycle checkpoint monitors the cell cycle.
G1 checkpoint Intra-S
Checkpoint
G1 checkpoints: Cells arrest in G1
Intra-s-phase checkpoint: DNA
synthesis slow down
G2 checkpoints: cells arrest in G2
phase
Spindle checkpoints: blocks the
transition from metaphase to
anaphase within mitosis.
G1
S
G2
G checkpoint
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If the checkpoint is bypassed
or destroyed, cells will:
Become cancerous
Undergo apoptosis (programmed
cell death)
M
Spindle checkpoint
G2 checkpoint

Tumor Suppressors
A tumor suppressor is a gene or gene product that reduces the
probability that a cell in a multicellular organism will turn into a
tumor cell.
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The functions of tumor suppressor proteins:
1. Repress the cell cycle if these genes are not expressed.
2. Couple the cell cycle to DNA damage.
3. Initiate apoptosis if DNA damage is not repairable
4. Involved in cell adhesion, inhibit metastasis.
Question: Review
Tight , Adheren, Gap junctions
and desmosomes are examples
of?
___________Cell:cell junctions
P i i li i b t
___________
___________
Close
Endocrine
Paracrine signaling is between
_____ cells.
Type of cell signaling that
acts at a distance.
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___________Kinase
Signal transduction molecule
that adds phosphates to
targets.
Cell signal can be amplified
via _________. ___________Signal transduction

Cell communication
uses cell junctions
d h i l
Cell communication
uses cell junctions
d h i l
Learning Summary
Signal Transduction
Secondary messenger
Signal Transduction
Secondary messenger
and chemical
signals.
and chemical
signals.
RTKs, GPCRs and
i t ll l t
RTKs, GPCRs and
i t ll l t
There are
Checkpoints and
There are
Checkpoints and
y g
y g
43/45
intracellular receptors
are types of signal
receptors.
intracellular receptors
are types of signal
receptors.
p
tumor suppressors
that control the cell
cycle.
p
tumor suppressors
that control the cell
cycle.
Congratulations
You have successfully completed theYou have successfully completed the
core tutorial
Cell Communication and
Cell Cycle
44/45

Wh t’ N t
Chemistry :: Biology :: Physics :: Math
What’s Next …
Step 1: Concepts – Core Tutorial (Just Completed)
Step 2: Practice – Interactive Problem Drill
Step 3: Recap – Super Review Cheat Sheet
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