1. Cell Communication

2. The “Cellular Internet”
All multicellular organisms must “communicate and cooperate” to maintain homeostasis
universal mechanisms of cellular regulation involve cell-to-cell communication.
Basically, a signal is received and then converted into a response within the cell

3. Methods used by Cells to Communicate
Cell Signaling using chemical messengers (proteins, steroids, etc)
Local signaling over short distances
Cell-Cell Recognition Proteins attached to cell exterior; glycolipids and glycoproteins (e.g. blood type proteins)
Local regulators (chem signals from the neighboring cells)
Paracrine- secreted signal (e.g. growth factors)
Synaptic- directed signal (e.g.neurotransmitter)
Long distance signaling
Hormones

4. Cell-Cell Communication
Transport between cells
cell junctions are protein tunnels directly connecting adjacent cells (called gap junctions in animal cells & plasmodesmata in plants); allow material to pass through (e.g. chem signals or water)
Plasma membranes
Plasmodesmata
between plant cells
Gap junctions
between animal cells
Figure 11.3
(a) Cell junctions. Both animals and plants have cell junctions that allow molecules
to pass readily between adjacent cells without crossing plasma membranes.

5. Local Signaling Example: Cell-Cell Recognition
Used to guard against unfamiliar cells and invaders; part of immune response
Membrane bound cell surface molecules
Glycoproteins
Glyolipids
Figure 11.3
(b) Cell-cell recognition. Two cells in an animal may communicate by interaction
between molecules protruding from their surfaces.

6. Local Signaling Example: Local Regulators
- Communicate with neighbors using local regulators, only work over a short distance
- Paracrine signaling communicates with all cells surrounding (e.g. growth factor to stimulate mitosis near a wound)
- Synaptic signaling is directed to one neighbor cell (e.g. neurotransmitters from one neuron to the next)
(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.
(b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.
Local regulator
diffuses through
extracellular fluid
Target cell
Secretory
vesicle
Electrical signal
along nerve cell
triggers release of
neurotransmitter
Neurotransmitter
diffuses across synapse
is stimulated
Local signaling

7. Long-distance Signaling Example: Hormones
long-distance signaling used by both plants and animals; hormones (natural steroids) are released into bloodstream by glands and can go anywhere in the body causes changes in a lot of cells simultaneously (e.g. adrenaline)
Hormone travels
in bloodstream
to target cells
(c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood Hormones may reach virtually all body cells.
Long-distance signaling
Blood
vessel
Target
cell
Endocrine cell
Figure 11.4 C

8. Long-Distance Signaling Systems
Nervous System (Animals only)
Quick long distance communication through Electrical signals sent through neurons
Endocrine System (Animals only)
Glands that secrete hormones into cell spaces or into blood stream (lymph nodes, adrenal gland, pituitary gland, etc)
Note: Plants also use hormones
Transported through vascular system, plasmodesmata, or released into air (e.g. ripening fruit)

9. The Three Stages of Cell Signaling
All cell signaling (long or short distance) occurs in three stages
Reception – receive the signal
Transduction – signal causes a cascade of communication inside the cell
Response – cell responds to the signal
Called Signal transduction pathways
Note: Pathways are similar in all life, supporting evolution

10. Overview of cell signaling
EXTRACELLULAR
FLUID
Receptor
Signal
molecule
Relay molecules in a signal transduction pathway
Plasma membrane
CYTOPLASM
Activation
of cellular
response
Figure 11.5
Reception 1
Transduction 2
Response 3

11. Stage One: Reception
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane 1 1
Reception
The receptor and signaling molecules fit together (lock and key model, induced fit model, just like enzymes!)
Receptor
Signaling
molecule
The signaling molecule (a ligand) binds to the specific receptor protein; shape determines function!

12. Stage Two: Transduction
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane 1 1
Reception 2
Transduction
Receptor
2nd Messenger!
Relay molecules in a signal transduction pathway
Signaling
molecule
Reception sets off a relay team of communication proteins in the cell; second messengers carry the original exterior signal to the inside of the cell

13. Stage Three: Response
EXTRACELLULAR
FLUID
CYTOPLASM
Plasma membrane 1
Reception 2
Transduction 3
Response
Receptor
Activation
of cellular
response
Relay molecules in a signal transduction pathway
Can be catalysis, activation of a gene, triggering apoptosis, almost anything!
Signaling
molecule
The cell will respond to the signal as directed (e.g. make a protein, produce more energy, enter mitosis, etc.)

14. Signal Transduction Animation

15. Common Receptor Proteins (stage one)
G-protein coupled receptors
Receptor tyrosine-kinases
Ion channel receptors

16. G-Protein Coupled Receptors are often involved in diseases such as bacterial infections.
G-Protein Receptors
Inactive
enzyme
Plasma
membrane
G protein-coupled
receptor
Activated
receptor
Signaling molecule
Enzyme
GDP 1 2
GDP
GTP
CYTOPLASM
G protein
(inactive)
Activated
enzyme i
GTP
GDP P 3 4
Cellular response

17. Receptor tyrosine kinases
Signal molecule
Signal-binding site
CYTOPLASM
Tyrosines
Signal molecule
Helix in the
Membrane
Tyr
Dimer
Receptor tyrosine kinase proteins (inactive monomers) P
Cellular response 1
Inactive relay proteins
Activated relay proteins
Cellular response 2
Activated tyrosine-
kinase regions
(unphosphorylated
dimer)
Fully activated receptor
tyrosine-kinase
(phosphorylated
6 ATP ADP
Figure 11.7

18. Ion Channel Receptors Very important in the nervous system
Gate
closed 1
Ions
Very important in the nervous system
Creates an action potential
Signal triggers the opening of an ion channel
Opening the channel allows ions to rush down a concentration gradient, creating an electrical signal from the moving charges
Signaling
molecule
(ligand)
Ligand-gated
ion channel receptor
Plasma
membrane 2
Gate open
Cellular
response 3
Gate closed

19. Notes about Transduction
Reminder, Transduction is the second stage. It occurs when cascades of molecular interactions relay signals from the receptor to the target molecules inside the cell
It is a multistep pathway
can amplify a signal and create a large response from a single ligand
Requires communication and coordination within the cell itself
Transduction Example: Protein Phosphorylation

20. Protein Phosphorylation and Dephosphorylation
Protein Phosyphorylation cascade - An example of transduction in which a series of protein kinases add a phosphate to the next one in line, activating it, and sending the signal to the target (like a bucket brigade!)
enzymes then remove the phosphates to reset the cascade after “Response” stage

21. A phosphorylation cascade
Signal molecule
Active
protein
kinase 1 2 3
Inactive
protein kinase
Cellular
response
Receptor P
ATP
ADP PP
Activated relay
molecule i
Phosphorylation cascade P 
A relay molecule
activates protein kinase 1. 1 2
Active protein kinase 1
transfers a phosphate from ATP
to an inactive molecule of
protein kinase 2, thus activating
this second kinase.
Active protein kinase 2
then catalyzes the phos-
phorylation (and activation) of
protein kinase 3. 3
Enzymes called protein
phosphatases (PP)
catalyze the removal of
the phosphate groups
from the proteins,
making them inactive
and available for reuse. 5
Finally, active protein
kinase 3 phosphorylates a
protein (pink) that brings
about the cell’s response to
the signal. 4
Figure 11.8

22. Small Molecules and Ions as Second Messengers
Transduction Example:
Secondary messengers: small, nonprotein, water-soluble molecules or ions that act as secondary messengers to carry the signal to the target (example- cyclic AMP)
(Note: Membrane Proteins would be the primary messengers since they get the signal first)

23. Cyclic AMP
cAMP is often found with the G-protein receptors; made from ATP that has only one phosphate; secondary messenger
ATP
GTP
cAMP
Protein
kinase A
Cellular responses
G-protein-linked
receptor
Adenylyl
cyclase
G protein
First messenger
(signal molecule
such as epinephrine)
Figure 11.10

24. Cyclic AMP Cyclic AMP (cAMP) Is made from ATP O –O N O P OH CH2 NH2
H2O HO
Adenylyl cyclase
Phoshodiesterase
Pyrophosphate
Cyclic AMP
AMP i

25. Ex Diagram: Transduction in a G-protein pathway using cAMP
Fig
First messenger
Adenylyl
cyclase
G protein
G protein-coupled
receptor
GTP
ATP
Second
messenger
cAMP
Ex Diagram: Transduction in a G-protein pathway using cAMP
Protein
kinase A
Cellular responses

26. Second Messenger Example: Calcium Ions
Calcium ions act as a secondary messenger in many different pathways because cells can regulate its concentration and location
EXTRACELLULAR
FLUID
Plasma
membrane
ATP
CYTOSOL
Ca2+ pump
Endoplasmic
reticulum (ER)
Nucleus
Mitochondrion
Key
High [Ca2+]
Low [Ca2+]
Other secondary messengers trigger the release of concentration gradients of Ca2+ in various areas of the cell, creating moving charges and electrical signals. Pumps then reset the Ca2+ concentration gradient to be used again.

27. Calcium Ion Diagram example3 2 1
IP3 quickly diffuses through
the cytosol and binds to an IP3–
gated calcium channel in the ER
membrane, causing it to open. 4
The calcium ions
activate the next
protein in one or more
signaling pathways. 6
Calcium ions flow out of
the ER (down their con-
centration gradient), raising
the Ca2+ level in the cytosol. 5
DAG functions as
a second messenger
in other pathways.
Phospholipase C cleaves a
plasma membrane phospholipid
called PIP2 into DAG and IP3.
A signal molecule binds
to a receptor, leading to
activation of phospholipase C.
EXTRA-
CELLULAR
FLUID
Signal molecule
(first messenger)
G protein
G-protein-linked
receptor
Various
proteins
activated
Endoplasmic
reticulum (ER)
Phospholipase C
PIP2
IP3
(second messenger)
DAG
Cellular response
GTP
Ca2+
(second
messenger)
IP3-gated
calcium channel
Figure 11.12

28. Cellular Response (Stage 3)
Signaling
molecule
Cellular Response (Stage 3)
Specificity of the signal
The same signal molecule can trigger different responses depending on other signals and various receptor proteins or SMs
Many responses can come from one signal!
Receptor
Relay
molecules
Response 1
Response 2
Response 3
Cell A. Pathway leads
to a single response.
Cell B. Pathway branches,
leading to two responses.

29. The signal can also activate, inhibit ,or create multiple responses from one signal
Activation
or inhibition
Response 4
Response 5
Cell C. Cross-talk occurs
between two pathways.
Cell D. Different receptor
leads to a different response.

30. Response example- cell signaling leads to regulation of transcription (turn genes on or off)

31. Long-distance Signaling Response Example
Some hormones induce transcription. Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated. (ex: testosterone, which is a transcription factor)

32. Termination of Communication
Response is terminated quickly by the reversal of ligand binding

33. Any Questions??
Can You Hear Me Now?

34. Two body systems control MOST communication
1. Nervous System – uses ion concentration gradients and action potentials to communicate quickly through electrical impulses and neurons
2. Endocrine System - uses hormones secreted into the bloodstream (faster, further reach) or surrounding cell space; slower than nervous system, but longer lasting effect

35. Human Endocrine System

36. Major Vertebrate Endocrine Glands Their Hormones (Hypothalamus–Parathyroid glands)36

38. Each system affects the output of the other
Each system affects the output of the other. Feed back is another common feature.
Neurosecretory cells in endocrine organs and tissues secrete hormones. These hormones are excreted into the circulatory system (ex. Adrenaline) or the surrounding cell space (ex. Lymph). 38

39. Stress and the Adrenal Gland
Are the following hormone pathways Positive or Negative Feedback systems?
Stress and the Adrenal Gland

40. 40

41. 41

42. Answers
Stress and Adrenaline – Positive Feedback (induces a response/change)
Calcium and Blood Sugar regulation – Negative Feedback (prevents a change, maintains a normal level)