Lecture 7:

Cell
Communication

Cell Communication
• Cell Communication
– Types
– Ligand/Receptor Interactions
– Hormone Signaling

1
 Cell Communication
• Each cell in the body is able to function as a single living unit BUT
must also communicate with nearby cells to maintain homeostasis
and perform specialized functions
• Types of Cell Communication
– Cell Junctions
– Cell to Cell Recognition
– Chemical Signals
• Paracrine
• Autocrine
• Neurotransmitters
• Hormones

Cell Junctions
• Cells can be directly linked together
by cellular junctions
• Cell Junctions:
– Desmosomes: anchor two cells
together with cell-adhesion
molecules (CAMs), prevents
over-stretching of tissue
– Tight Junctions: seal two cells Desmosome
Tight Junction
together with small proteins,
prevents leakage between
cells, forms tight barriers
– Gap Junctions: cytoplasm of
cells is directly linked by
connexon protein “tunnels”,
allows direct communication
between cells
Gap Junction

2
 Cell 1 cytosol Cell 2 cytosol
Plaque
(cytoplasm
thickening) Desmosome

Cadherins
(cell adhesion
molecules)

20 nm

Keratin
(intracellular Desmosome
intermediate
cytoskeletal Interacting plasma
filaments) membranes
Fig. 3-4, p. 62

Cell 1 cytosol Cell 2 cytosol

Strands
of occludin
proteins

Kiss site
Tight
Tight
junction
junction

Intercellular
space

Interacting
plasma
Tight Junction membranes
Fig. 3-5b, p. 63

3
 Cell 1 cytosol Cell 2 cytosol

Connexon

Gap junction

Diameter of Longitudinal section

channel = 1.5 nm of connexon
PASSAGE OF
IONS AND SMALL
MOLECULES
NO PASSAGE
OF LARGE
MOLECULES

2–4 nm

Gap Junction Interacting

plasma
membranes Fig. 3-6, p. 64

Gap Junctions
• Gap Junctions: cytoplasm of cells is
directly linked by connexon protein
“tunnels”, allows direct Connexon
communication between cells
• Allows ions and small water
soluble chemicals to pass PASSAGE OF
IONS AND
between cells SMALL
MOLECULES
• causes multiple cells to work
together as a single functional
unit, shared intracellular signals
• example: synchronized
contraction of cardiac muscle
Interacting
cells, smooth muscle cells plasma
membranes

4
 Gap Junctions
Small molecules and ions

Fig. 4-20a, p. 117

Cell to Cell Recognition

• Cells membranes have surface carbohydrate molecules
(glycoproteins, glycolipids) that can signal to other cells
• example: self vs. non-self recognition of cells by immune system
• example: boundaries of tissues delineated to mark cell tissue
type and prevent invasion of other tissues
Carbohydrate
chain
Glycolipid

Glycoprotein

10

5
 Cell to Cell Recognition

(b) Transient direct linkup of cells’ surface markers

Fig. 4-20b, p. 117

11

Chemical Signaling
• Cells can communicate without directly connecting or touching,
using local and long-distance chemical signals
• Chemicals will be secreted by one cell and target to another cell
• This usually requires a ligand à receptor interaction

12

6
 Ligands & Receptors
• Ligands: extracellular chemicals that act
as chemical signals, signaling molecules

• Receptors: specific proteins on the

target cell membrane that recognize and
bind to ligands
– receptors recognize specific ligands or groups
of ligands, this binding is specific
– multiple types of receptors may recognize
one ligand, each having a different effect on a
cell

13

Types of Receptors

14

7
 Types of Chemical
Signals
• Local chemical signals:
– Autocrine
– Paracrine
– Neurotransmitters
• Long-Distance chemical signals
– hormones
– neurohormones

15

Paracrine & Autocrine Signals

• Paracrine Signals – ligand is released and diffuses nearby to affect cells
in the local area
• Autocrine Signals – ligand is released and affects the same cell that
released it
– Examples: histamine, cytokines, prostaglandins

16

8
 Paracrine Signals
Secreting cell Local target cell

Paracrine
(c) Paracrine secretion

Fig. 4-20c, p. 117

17

Neurotransmitters
• Neurotransmitters – secreted by one neuron, diffuses across
synapse to affect the adjacent neuron/gland/muscle
– local, fast, short-lived

18

9
 Neurotransmitters

Local target cell

Electrical signal

Secreting cell
(neuron)
Neurotransmitter
(d) Neurotransmitter secretion

Fig. 4-20d, p. 117

19

Hormones & Neurohormones

• Hormones – endocrine glands secrete chemicals into the blood to
travel to distant target cells
• Neurohormones – neurons secrete chemicals into the blood to
travel to distant target cells
• NOTE: cell must have the specific receptor on its membrane in
order to respond!

20

10
 Secreting cell
(endocrine cell)
Blood
Hormones

Hormone

Distant target cell

Nontarget cell
(no receptors)

(e) Hormonal secretion

Fig. 4-20e, p. 117

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Neurohormones
Neurohormone
Blood

Electrical signal

Secreting cell Distant target cell

(neuron)

Nontarget cell
(no receptors)

(f) Neurohormone secretion

Fig. 4-20f, p. 117

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11
 Cellular Effects
• Some chemical signals cannot enter the cell, and only act through
receptors:
– Chemical Signals will bind to target cell receptors
– The response will depend on the receptor AND the molecules inside of the
target cell
• Some chemical signals can enter the cell and the cell nucleus
– DNA, protein synthesis, and/or RNA can be affected directly

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Examples of Cellular Effects

• Examples of target cell responses to a chemical signal:
– Activate or inhibit enzyme activity
– Increase or Decrease protein synthesis through activation of
transcription factors
– Stimulate cell division and growth
– Alter electrical gradients– opening/closing of ion channels
(membrane potential/electrical potential)

24

12
 Types of Hormones
• Cells produce many types of hormone chemical signals from
different macromolecules and building blocks

• Water soluble (polar) hormones bind to receptors on the plasma

membrane, Lipid soluble (non-polar) hormones can enter the cell
and bind to intracellular receptors

1. Hydrophilic (water-soluble) hormones

2. Lipophilic (lipid-soluble) hormones

25

Water Soluble vs. Lipid Soluble Hormones

• Water Soluble Hormones: transported dissolved in the blood
plasma, bind to extracellular plasma membrane receptors
– Amine Hormones – amino acid derivatives
• epinephrine, T3, T4, serotonin, melatonin
– Peptide Hormones – proteins
• Vasopressin, insulin
• Lipid Soluble Hormones: circulate bound to plasma proteins such
as albumin, bind to intracellular receptors
– Steroid Hormones – cholesterol based
• Cortisol, aldosterone, estrogen, testosterone
– Eicosanoid Hormones –derived from omega-3/omega-6 fatty acids
• Prostaglandins, leukotrienes

26

13
 Water Soluble Hormones
• Water soluble hormones- utilize an
extracellular membrane bound
receptor
• Binding of hormone causes a
conformational change in the receptor
which will change something inside the
cell, usually the activity of a protein or
group of molecules
• The extracellular signal is transduced to
an internal change
• “signal transduction”

27

Lipid Soluble Hormones

• Lipid soluble hormones
– Can pass through the plasma
membrane
– bind to an intracellular receptor
in the nucleus to alter protein
synthesis
– can increase or decrease protein
synthesis directly

28

14
 Receptor Types
• Ultimately, the effect of a hormone or other ligand on a cell
depends on the type of receptor that it activates
• There are 4 main types of receptors
1. Receptor ion-channel
2. Receptor enzymes
• Tyrosine Kinase Receptors
3. G-protein coupled Receptors
• cAMP Pathway
• Ca/Calmodulin Pathway
4. Intracellular Receptors

29

1
Ion

Receptor Ion Channels Receptor

channel Extracellular
messenger

• Receptor Ion channel:

– the receptor IS an ion channel
2
– ligand (extracellular messenger) binds to
receptor
– the receptor changes shape, opens to allow
specific ions in
– ions enter the cell, causing a change in cellular 3
activity Ion
entry

(perhaps 4
through
multiple
steps)

Cellular response
Fig. 4-22a, p. 119

30

15
 Extracellular
messenger 1

Receptor Enzymes Receptor

enzyme

• Receptor Enzymes:
• The receptor has an enzyme
Active
attached to its internal surface protein 2
kinase
• the ligand (extracellular site
messenger) binds, causing a (perhaps
change in enzyme shape through
multiple
• the enzyme becomes active and steps) 3
catalyzes a specific chemical
reaction, such as Active
phosphorylation of a protein designated
protein
• the downstream molecules
4
become active changing activity
in the cell
Cellular response
Fig. 4-22b, p. 119

31

Extracellular messengers

Tyrosine Kinase (signal molecules)

Receptors Tyrosine
kinase
receptor-
enzyme
ECF
• Tyrosine Kinase Receptors: Plasma
• The receptor has tyrosine membrane

kinase enzyme attached to its ICF

internal surface
• the ligand (extracellular Protein
messenger) binds, activating kinase
sites
the tyrosine kinases (active)
• tyrosine kinases
phosphorylate proteins to Inactive (changes Active
activate them designated shape and designated
protein function) protein
• the active proteins change
cellular activity KEY

= Phosphate Cellular
Tyr = Tyrosine response
Fig. 4-23, p. 120

32

16
 1
G-protein coupled Extracellular (first) messenger
G-protein-coupled receptor ECF

Receptors Plasma
membrane
• G-protein coupled receptors: ICF
Active 3 Effector
• The receptor has a G-protein 2 G protein
protein
attached to its internal
surface Second
4 messenger
• the ligand (extracellular
messenger) binds, activating
a g-protein 5 Active
protein
• G-protein activates an kinase
effector protein (perhaps
6 through
• The effector protein multiple
produces a second steps)

messenger causing a second Active

designated
messenger cascade 7 protein

Cellular response
Fig. 4-22c, p. 119

33

Second Messenger Cascades

• Two main types of second messengers are used downstream of G-
protein coupled receptors

1. cyclic AMP (cAMP)

2. Calcium (Ca2+)

34

17
 cAMP Pathway
• ligand: water soluble
• receptor: extracellular g-protein coupled receptor
• effector: Adenylate Cyclase (AC)
• 2nd messenger: cAMP
• downstream effects:
• activates protein kinase A enzyme
• pkA phosphorylates and activates cellular proteins
• cellular activity changes

35

Extracellular (first) messenger

(Activates)
GDP GTP
ECF
Plasma
membrane

cAMP G-protein- (Activates)

Adenylyl cyclase
(effector protein)
ICF

coupled

2nd receptor
G-protein-
Second
messenger

messenger
intermediary
2
1

Pathway 3

Inactive Active
protein protein
kinase A kinase A

Inactive
designated Active
(changes designated
protein
shape and protein
function)

5
Key
Phosphate Cellular
response
Fig. 4-25, p. 125

36

18
 Ca/Calmodulin Pathway
• ligand: water soluble
• receptor: extracellular g-protein coupled receptor
• effector: phospholipase C
• phospholipase C converts PIP2 to IP3 and DAG, causing calcium
release
• 2nd messenger: Ca2+
• downstream effects:
• forms calcium/calmodulin (cAM) complex
• activates cAM kinase enzyme
• cAM kinase phosphorylates proteins in the cell
• cellular activity changes

37

Extracellular (first) messenger

(Activates) PIP2 (a component of
GDP GTP the phospholipid tails)

G-protein
coupled 2
receptor (Activates)
G-protein Active (Second
intermediary messenger)
phospholipase C
1 (effector protein)

Ca/Calmodul 3a
(Second
messenger)
from
ER

in 4a

2nd Inactive
calmodulin Active Ca2+–
calmodulin

messenger 5a

Inactive
complex

Active

Pathway CaM
kinase
CaM
kinase

6a
Inactive Active
designated (changes
protein designated
shape and protein
function)

7a
Cellular response Fig. 4-26, p. 126

38

19
 DAG Activity
• ligand: water soluble
• receptor: extracellular g-protein coupled receptor
• effector: phospholipase C
• phospholipase C converts PIP2 to IP3 and DAG, causing calcium
release
• ***** DAG also has its own activity as a 2nd messenger
• 2nd messenger: DAG
• downstream effects:
• activates protein kinase C enzyme
• pkC phosphorylates proteins in the cell
• cellular activity changes

39

Signal Amplification

• Signal Amplification: The binding of a single

ligand to a G-protein coupled receptor can
trigger thousands of molecular changes
downstream via the 2nd messenger cascades

40

20
 Signal Amplification
Molecules in
second-
messenger Total number
system of molecules

Extracellular chemical
messenger bound to 1
membrane receptor
Activated Amplification
10
adenylyl cyclase (10)

Amplification
Cyclic AMP
(100)

Activated 1000
protein kinase

Phosphorylated
(activated) protein Amplification 100,000
(e.g., an enzyme) (100)

Products of Amplification
(100) 10,000,000
activated enzyme

Fig. 4-27, p. 127

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Blood vessel

Intracellular
Plasma
protein
carrier
Steroid

Receptors
ECF hormone
Plasma
membrane

• Intracellular receptors: Cytoplasm Cellular response

• The receptor is inside the cell 1

9

• a lipid soluble hormone Portion

that binds
New
protein
Steroid
enters the cell and binds to a hormone
receptor
hormone
Portion
8

receptor IN the cytoplasm or that binds

to DNA

nucleus, forming a Hormone 2 7

Response Element (HRE)
DNA-binding
• The HRE binds to DNA and site (active)

alters transcription of a
particular gene 6
3
• Protein synthesis of that mRNA 5
gene changes to change 4
activity in the cell DNA

Hormone Gene
response
Nucleus element
Fig. 4-28, p. 128

42

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