Cell Communication

The Cellular “Internet” Within multicellular organisms, cells

must communicate with one another to coordinate their activities

A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response

Signal transduction pathways are very similar in all organisms, even organisms as different as unicellular yeasts and multicellular mammals

Local (Short-Distance) Signaling Cells may communicate by direct contact

Plasmodesmata in plant cells Gap junctions in animal cells

Animal cells can also use cell-cell recognition Membrane-bound surface molecules can interact and

communicate

Local (Short-Distance) Signaling Messenger molecules can also be secreted by the signaling cell Paracrine signaling:

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

Example: growth factors Synaptic Signaling:

Nerve cells release chemical messengers (neurotransmitters) that stimulate the target cell

Long-Distance SignalingEndocrine

(hormone) signaling Specialized cells

release hormone molecules, which travel (usually by diffusion through cells or through the circulatory system) to target cells elsewhere in the organism

The Three Stages of Cell Signaling There are 3 stages at the “receiving end”

of a cellular conversation:1. Reception2. Transduction3. Response

Stage 1: Reception The target cell “detects” that there is 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 (receptor protein) The signal molecule “searches out” specific receptor

proteins The signal molecule is a ligand

It is a molecule that specifically binds to another one and induces a change in the shape of the receptor protein

Ligands can be hydrophobic or hydrophillic

Receptor proteins There are 2 different types of receptor proteins:

Membrane receptors: transmembrane proteins Intracellular receptors: proteins that occur in the

cytoplasm or the nucleus

Second messengers Molecules that relay messages from

membrane receptors to other molecules They are all:

Small, nonprotein molecules Either hydrophillic, hydrophobic, or gaseous Ex. Ca ions, IP3, CAMP, and DAG

Stage 2: Transduction This stage converts the signal into a form

that can bring about a specific cellular response One signal-activated receptor activates another

protein, which activates another molecule, etc., etc. - this is called a signaling cascade

These act as relay molecules Often the message is transferred using protein

kinases, which transfer phosphate groups from ATP molecules to proteins

These can be very complicated

Stage 2: Transduction

Advantages of signal transduction Amplification: the effect of the signaling

molecule can be amplified Control: the cell can control the

accuracy of the signaling Multiplicity: a signaling molecule can

start many different processes at once to respond to the signal

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 mRNA

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

Receptors and their responses

Receptor Receptor description

Ligand(1st messengers)

Supporting mechanisms

Cellular response examples

Gated ion receptor

Types: *ligand gated ion receptor

*Voltage gated ion receptor

Ligand: Acetylcholine

Voltage: Change in membrane voltage

None Ligand: Na+ gate opens; nerve impulse or muscle contraction

Voltage: Na, K gates open, nerve transmission

Receptors and their responses

Receptor Receptor description

Ligand(1st messengers)

Supporting mechanisms

Cellular response examples

G Protein – Coupled Receptor (GPCR)

GPCR + Gprotein + Effector protein

Various *Enzymatic effector protein

2ndmessengers:cAMPIP3 / DAGCa2+

*EEF: enzyme activity

cAMP: glycogen glucose

IP3 releases Ca2+ as a second messenger Ca2+ causes muscle contraction

Receptors and their responses

Receptor Receptor description

Ligand(1st messengers)

Supporting mechanisms

Cellular response examples

Protein Kinase Receptor

Types: *Receptor Tyrosine Kinase (RTK)

*Receptor Serine/Threonine Kinase

RTK: Insulin

RS/TK: Mitogens, growth factors

RTK: multiple kinase cascadesRS/TK:Ras (g protein):Mitogen – kinasecascade

RTK: glucose to glycogen

RS/TK: Activation of transcription factors that promote growth and cell differentiation

Receptors and their responses

Receptor Receptor description

Ligand(1st messengers)

Supporting mechanisms

Cellular response examples

Intracellular receptor

Cytoplasmic or nuclear receptors

Steroid hormones (testosterone& estrogen)

Development of primary and secondary sex characteristics

When cell signaling doesn’t work

Signal transduction pathways can be blocked or defective

Examples: Diabetes Cholera Autoimmune disease Cancer Neurotoxins, poisons, pesticides Drugs (anesthetics, antihistamines, blood

pressure meds)

Cholera

Disease acquired by drinking contaminated water (w/human feces)

Bacteria (Vibrio cholerae) colonizes lining of small intestine and produces toxin

Toxin modifies G-protein involved in regulating salt & water secretion

G protein stuck in active form intestinal cells secrete salts, water

Infected person develops profuse diarrhea and could die from loss of water and salts

Apoptosis = cell suicideCell is dismantled and digestedTriggered by signals that activate

cascade of “suicide” proteins (caspase)Why?

Protect neighboring cells from damageAnimal development & maintenance

May be involved in some diseases (Parkinson’s, Alzheimer’s)

Interference may contribute to cancers

Apoptosis of a human white blood cell

Left: Normal WBCRight: WBC undergoing apoptosis – shrinking and forming lobes (“blebs”)

Effect of apoptosis during paw development in the mouse

Drugs There are drugs that interfere with cell

signaling can either be agonists or antagonists Agonists: acts the same way that a ligand

does Antagonists: blocks the binding site of the

receptor and does not let cell signaling occur Ex. The poison curare blocks the binding

sites for the chemical acetylcholine which will cause muscle paralysis and death