Cell Communication

Objectives:

Short distance communication – autocrine (synapse), paracrine

Long distance communication – endocrine

Three types of protein communicators – TKR, Channels, G protein coupled receptors

Three stages of signaling – reception, transduction, response

The Cellular “Internet”

Multicellular organisms: cells must communicate with one another

to coordinate their activities

Unicellular organisms: communication also important

Signal transduction pathway: a series of steps signal on a cell’s surface specific cellular response

Similar in all organisms

•Embryonic Development

•Immune Response

Local (Short-Distance) Signaling

Direct contact Plasmodesmata in plant cells

Gap junctions in animal cells

Local (Short-Distance) Signaling Direct contact Plasmodesmata in plant cells

Gap junctions in animal cells

What membrane associated molecule

plays a role in cell-cell recognition?

Cell-cell recognition Membrane-bound surface molecules can interact &

communicate

Signals can pass between adjacent cells through junctions

•Glycoproteins

•Antigens

Cell-cell Recognition

Glycoproteins

Cell-Cell Recognition

Antigens

Immune System

Blood Types

Cell-Cell Recognition

Receptors

Local (Short-Distance) Signaling

Messenger molecules can be secreted by the signaling cell Paracrine signaling:

One cell secretes (releases) molecules that act on nearby “target” cells

Ex: growth factors (stimulate nearby cells to grow & multiply)

Synaptic Signaling: Nerve cells release chemical messengers (neurotransmitters)

that stimulate the target cell

Paracrine Neurotransmitters

Distinguish

between

autocrine

and

paracrine

signaling

Long-Distance Signaling Endocrine (hormone) signaling Specialized cells release hormone

molecules

hormones travel to target cells

elsewhere in the organism

Ex. Insulin

Ex. Ethylene

How do hormones get into blood vessel?

How do hormones get to target?

diffusion

circulatory system

Unlike other plant hormones,

ethylene is a gaseous hormone

ripening

Endocrine

Paracrine Autocrine

Exocrine

Secrete their products

into ducts (duct

glands) which lead

directly into the

external environment.

http://www.wikipedia.org/wiki/Duct_(anatomy)

Exocrine

Pancreas

Sweat glands

Mammary glands Salivary glands

Secrete product into ducts

Examples: sweat glands,

salivary glands, mammary

glands, stomach, liver,

pancreas.

http://www.wikipedia.org/wiki/Sweat_glandhttp://www.wikipedia.org/wiki/Salivary_glandhttp://www.wikipedia.org/wiki/Mammary_glandhttp://www.wikipedia.org/wiki/Mammary_glandhttp://www.wikipedia.org/wiki/Stomachhttp://www.wikipedia.org/wiki/Liverhttp://www.wikipedia.org/wiki/Pancreas

The Three Stages of Cell Signaling The “receiving end” of a cellular conversation:

1. Reception 2. Transduction 3. Response

The Three Stages of Cell Signaling

The “receiving end” of a cellular conversation:

1. Reception 2. Transduction 3. Response

DO NOW:

Describe the 3 stages of cell signaling.

Stage 1: Reception Target cell “detects” a signal molecule coming from

outside the cell The signal is detected when it binds to a protein on the cell’s

surface or inside the cell

The signal molecule “searches out” specific receptor proteins The signal molecule is a ligand

• It is a molecule that specifically binds to another one (think enzymes!)

http://www.youtube.com/watch?v=bU4955rLv_8&feature=player_embedded

http://www.youtube.com/watch?v=2bbBrpgeheY&feature=related

http://www.youtube.com/watch?v=bU4955rLv_8&feature=player_embeddedhttp://www.youtube.com/watch?v=2bbBrpgeheY&feature=related

Stage 2: Transduction

The signal is converted into a form that can bring about a specific cellular response One signal-activated receptor activates another

protein, which activates another molecule, etc.

These act as relay molecules

Often the message is transferred using protein kinases

protein kinases: transfer phosphate groups from ATP molecules to proteins

http://www.youtube.com/watch?v=3jMBNesc-8k (dom)

http://www.youtube.com/watch?v=VoJVBqZ7X3I

http://www.youtube.com/watch?v=3jMBNesc-8khttp://www.youtube.com/watch?v=3jMBNesc-8khttp://www.youtube.com/watch?v=3jMBNesc-8khttp://www.youtube.com/watch?v=VoJVBqZ7X3I

Stage 2: Transduction

http://www.youtube.com/watch?v=MNVB7K-MDws

http://www.youtube.com/watch?NR=1&v=NaOBRvAFiJQ

http://www.youtube.com/watch?v=MNVB7K-MDwshttp://www.youtube.com/watch?v=MNVB7K-MDwshttp://www.youtube.com/watch?v=MNVB7K-MDws

Stage 3: Response

The signal that was

passed through the

signal transduction

pathway triggers a

specific cellular

response Examples: enzyme action,

cytoskeleton rearrangement,

activation of genes, etc., etc.

Diagram example:

transcription of DNA to

mRNA

Tyrosine Kinase Receptors

http://faculty.plattsburgh.edu/donald.slish/PIKactin.html

http://faculty.plattsburgh.edu/donald.slish/PIKactin.htmlhttp://faculty.plattsburgh.edu/donald.slish/PIKactin.html

Transduction

Ligand Binding & Downstream Events http://faculty.plattsburgh.edu/donald.slish/woc/RAS.html View animation at site:

http://faculty.plattsburgh.edu/donald.slish/animations.html

http://faculty.plattsburgh.edu/donald.slish/woc/RAS.htmlhttp://faculty.plattsburgh.edu/donald.slish/woc/RAS.htmlhttp://faculty.plattsburgh.edu/donald.slish/animations.html

Ion Channels http://faculty.plattsburgh.edu/donald.slish/Fig%203-9B.html View animations at site:

Ionotropic Receptor: ion channel;

requires binding of molecule (green)

to open channel to allow ions (red)

to flow through

Metabotropic Receptor: ion channel;

requires activation of a coupled receptor

to open channel to allow ions to flow

through

http://faculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlfaculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlfaculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlfaculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlfaculty.plattsburgh.edu/donald.slish/Fig 3-9B.html

Ion Channels

Ion Channels

Ionotropic

View animations at sites

http://faculty.plattsburgh.edu/donald.

slish/Fig%203-9B.html http://faculty.plattsburgh.edu/donald.slish/Fi

g%203-11A.html

Metabotropic

http://faculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-9B.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-11A.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-11A.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-11A.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-11A.htmlhttp://faculty.plattsburgh.edu/donald.slish/Fig 3-11A.html

Regulation by chemical messengers

axon

endocrine gland

receptor proteins

target cell

Neurotransmitters released by neurons

Hormones release by endocrine glands

receptor proteins

hormone carried by blood

neurotransmitter

Lock & Key system

Action of protein hormones

activates enzyme

activates enzyme

activates enzyme

ATP

produces an action

P

1

2

3

cytoplasm

receptor protein

response

signal

secondary messenger system

signal-transduction pathway

acts as 2nd messenger

target cell

plasma membrane

binds to receptor protein

protein hormone

ATP activates cytoplasmic signal

cAMP

GTP

activates G-protein

transduction

nucleus

target cell

DNA mRNA

protein

blood

protein carrier

S

S

S

S

Action of lipid (steroid) hormones

binds to receptor protein

cytoplasm

becomes transcription factor

ex: secreted protein = growth factor (hair, bone, muscle, gametes)

2

4

6

cross cell membrane

1

steroid hormone

mRNA read by ribosome 5

plasma membrane

protein secreted 7

3

adrenal gland

Ex. Action of epinephrine (adrenaline)

activates protein kinase-A

activates glycogen phosphorylase

activates adenylyl cyclase

epinephrine

liver cell

released to blood

1

2 5

receptor protein in cell membrane

cytoplasm

6 glycogen

activates phosphorylase kinase

GTP

cAMP

4

activates G protein

ATP

glucose

activates GTP

3

signal

transduction

response 7

GDP

Benefits of a 2nd messenger system

Amplification!

signal

receptor protein Activated adenylyl cyclase

amplification

amplification

amplification

amplification

GTP G protein

product

enzyme

protein kinase

cAMP

Not yet activated

1

2

4

3 5

6

7

FAST response!

amplification

Cascade multiplier!

The Specificity of Cell Signaling

The particular proteins that a cell possesses determine which signal molecules it will respond to and how it will respond to them

Liver cells and heart cells, for example, do not respond in the same way to epinephrine because they have different collections of proteins

G protein-linked receptor

G Protein- Linked

Receptors

Transmembrane protein receptors that

interact (can bind) with a G protein

capable of binding GDP and GTP

An activated (GTP bound) G protein

subunit (3 subunits per G protein)

separates & ‘seeks’ a protein that can

then create a cascade of effects in the cell

G Protein-Linked

The same signal can have different effects in different tissues G protein-linked receptor

can activate an effector protein in one tissue type, but inhibit in another

Start here Or Start here

Do Now:

1. Explain why cells need to signal/ communicate?

2. How do multicellular organisms differ from single-celled?

3. Describe the 3 major types of signaling?

4. Describe the 3 stages in cell signaling?

5. Identify the 2 locations of receptors?

Second Messenger:

Released into cytoplasm, where they

may have numerous effects (ie.

interact with multiple target proteins)

NOT - typically ions or small, water-

soluble molecules (like cAMP)

Act as cofactors or allosteric

regulators

Amplify signals

Second Messenger:

Protein Kinase Cascades

‘Domino effect’ that results in signal

Why? At each step, modify an inactive protein

kinase into an active one; each can catalyze many phosphorylations of target proteins Again, by producing different target proteins in

different tissues, can have varying responses to the same signals

So, in Summary:

Signals are cues from the organism or environment & can be autocrine, paracrine, or endocrine (hormone)

Signal-transduction pathways consist of: a receptor, transduction, and an effect (response)

Receptors can be on the membrane (ion channels, protein kinases, G protein-linked) OR in the cytoplasm (lipid hormone receptor)

Transduction can be direct (on membrane) or indirect (utilizing second messengers); these and/or transduction cascades can amplify signals

Effects vary depending upon signal but often result in changes in transcription or enzyme activity

Cells can communicate directly via gap junctions (animal) or plasmodesmata (plant)

A signal transduction pathway has three stages 1. reception: Reception is the target cell’s detection of a

signaling molecule coming from outside the cell. A chemical signal is “detected” when the signaling molecule binds to a receptor protein located at the cell’s surface or inside the cell.

2. transduction: The binding of the signaling molecule changes the receptor protein in some way, initiating the process of transduction. The transduction stage converts the signal to a form that can bring about a specific cellular response.

3. response: In the third stage of cell signaling, the transduced signal finally triggers a specific cellular response. The response may be almost any imaginable cellular activity—such as catalysis by an enzyme (for example, glycogen phosphorylase), rearrangement of the cytoskeleton, or activation of specific genes in the nucleus.

G proteins

G protein-coupled receptor: A G protein-coupled receptor (GPCR) is a cell-surface transmembrane receptor that works with the help of a G protein.

G protein: Loosely attached to the cytoplasmic side of the membrane, the G protein functions as a molecular switch that is either on or off, depending on which of two guanine nucleotides is attached, GDP or GTP—hence the term G protein. (GTP, or guanosine triphosphate, is similar to ATP.)

GDP: When GDP is bound to the G protein, as shown above, the G protein is inactive. The receptor and G protein work together with another protein, usually an enzyme.