Chapter 11: Cell Communication

Word Roots:

liga- = bound or tied to

trans- = across

Ligand – a small molecule that specifically binds to a larger one.

Transduction – the transmission of external signals and conversion of a message inside of the cell

Signal Transduction Pathways•Local Signaling

•Direct contact

•Cell junctions

•Local Regulators

•Paracrine signaling

•Synaptic signaling

•Long Distance Signaling

•Hormones

•Nervous

Direct Contact

Evolution of Cell Signaling• Yeast cells

– Identify their mates by cell signaling

factorReceptor

Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.

1

Mating. Binding of the factors to     receptors induces changes      in the cells that     lead to their     fusion.

New a/ cell. The nucleus of the fused cell includes all the genes from the a and a cells.

2

3

factorYeast cell,mating type a

Yeast cell,mating type

a/

a

a

Figure 11.2

Local Signaling

•Less specific

•Growth factors

•More Specific

•Neurotransmitters

Long Distance Signaling •Very Specific

•Target specific cells

•Hormones (endocrine signaling)

•Nerves – electrical transmission of impulses

www.arikah.com

Three Stages of Cell Signaling•Earl W. Sutherland – 1971

•Signal Transduction Pathway for glycogen breakdown.

•Reception

•Target cell detects a signal molecule from outside the cell when a ligand binds to a receptor

•Transduction

• binding of signal molecule changes the shape of the receptor initiating transduction sequence of changes in a series of molecules

•Response

•Transduced signal triggers a specific cellular response

•Ex: catalysis of enzyme, activation of genes, etc..

http://pizaroscience.weebly.com/uploads/2/0/4/6/20462914/11_05cellsignaling_a.mpg

Three Stages of Cell Signaling

Step 1: Reception•Receptor Protein (conformational change)

•Membrane

•Cytoplasm

•Nucleus

•Signal Molecule

•Ligand (highly specific)

•Small/hydrophobic

•Ex: steroid hormones

•Large/water soluble

•Ex: epinepherine

http://highered.mheducation.com/sites/9834092339/student_view0/chapter9/mechanism_of_action_of_lipid-soluble_messengers.html

A hydrophobic ligand can readily cross the plasma membrane and bind to an intracellular receptor

Testosterone acts as a transcription factor

Three Main Types of Plasma Membrane Receptors

•G-Protein Linked

•Receptor Tyrosine Kinases

•Ion Channel

http://learn.genetics.utah.edu/content/cells/cellcom/

G-Protein Linked

Ex: Fight or Flight Response

Reception: Epinepherine targets liver and muscle cells

Transduction: activates glycogen phosphorylase

Response: break down glycogen into glucose

G-Protein Linked•Embryonic development, sensory reception, yeast mating factors, epinepherine, many other hormones and neurotransmitters

•GTP – guanosine triphosphate (a nucleiotide)

Inactive G protein Ligand binding receptor shape change inactive G protein binds GTP replaces GDP activating the G protein

Activated G protein dissociates from the receptor binds to an enzyme and alters its activity triggering the next step in the pathway

G protein acts as GTPase hydrolyzing GTP into inactive GDP shutting down pathway when ligan is not present

GTP

Adenylyl cyclase

GDP

GDP Pi

GTP

Signal transduction pathway initiated

Receptor Tyrosine Kinases •Kinase – enzyme that catalyzes the transfer of a phosphate group

•Tyrosine kinase – membrane receptors that attach phosphates to the amino acid, tyrosine

•Regulates growth and reproduction

•Multiple pathways stimulated

•Branched pathways (10+)

•Abnormal receptor tyrosine kinases may contribute to some kinds of cancer

Receptor Tyrosine Kinases

Ion Channel Receptors•Ligand-gated ion channels

•Nervous system

•Sodium –Potassium Pump

•Some channels are controlled by electrical signals instead of a ligand

•Na+ and Ca2+

Sodium Potassium Pump

Checkpoint

• Compare and contrast the three major types of membrane receptors.

Step 2: Transduction•Multi-step

•Amplifies signal – signal sent to multiple molecules

•Require Relay Molecules

•Protein Kinases – transfers phosphate groups from ATP to a protein

•Serine/threonine kinases (animals, plants, fungi)

•Phosphorylation cascade

•Conformational change

•Increase or decrease activity of the protein

•Protein Phosphatases – remove phosphates from proteins

•Recycle and reuse kinases (dephosphorylation)

Reception

Transduction

ResponsePhosphorylation Cascade

Second Messengers•Small, non-protein, water soluble molecules or ions

•Diffuse easily

•Easily Amplified

•Cyclic AMP (cAMP)

•Calcium ions (Ca2+)

•Inositol triphosphate (IP3)

•Diacylglycerol (DAG)

Cyclic AMP•Cyclic adenosine monophosphate

•Created by Adenylyl Cyclase from ATP

•Many cAMP molecules – amplification

•Phosphodiesterase

•Activates Protein Kinase A

‘Locking’ the pathway

Cholera – Vibrio cholerae

Locks G-Protein for water and salt regulation ‘on’

Unable to hydrolyze GTP into GDP = stuck in active form

Diarrhea

Vasodilatation

Cyclic GMP – relaxes artery walls

Viagra – blocks cyclic cGMP from breaking down into GMP

– increases blood flow, prolonging the signal

Calcium Ions and Inositol Triphosphate•Ca2+ low in cytosol, high in ER and ECF

•Active transport and membrane proteins

•Controlled by gated ion channels

•Regulates:

•Muscle contraction

•Secretion of other substances

•Cell division

•Used:

•G-protein

•Receptor Tyrosine Kinases

Step 3: Response•Cytoplasmic or Nuclear

•Regulates:

•Enzyme/Protein activity

•Enzyme/Protein creation

•Transcription factors

•Growth factors

•Hormones

Cytoplasmic Response

Nuclear Response

Benefits of Transduction Pathways•Signal Amplification

•Each step – more amplification

•Specificity

•Branched pathways – Receptor Tyrosine Kinases

Signaling Efficiency•Scaffolding Proteins

•Signaling Complexes

•Proteins can participate in:

•More than one pathway in 1 cell

•Many pathways in different cells

Step 4: Signal Termination•Reversible binding

•Signal molecule unbinds

•GTPase activity

•Phosphodiesterase

•Phosphatases