Ch 11: Cell communication 1st concept: External signals from other cells are converted into responses within a cell When does it start? ? Periferal protein and a ligand watch

Signal transduction pathways Can cause cellular responses using chemical signals that touch the surface of the cell… The chemistry is similar from microbes and mammals, suggesting an early origin of this biochemistry

Evolution of Cell Signaling Yeast cells Identify their mates by cell signaling Receptors Secrete mating factors. 1 Mating. New a/ cell. 2 3  factor Yeast cell, mating type a mating type   a/ a

Animal and plant cells, compared… Have cell junctions that directly connect the cytoplasm of adjacent cells, allowing communication Plasmodesmata Gap junctions Cell junctions.

animal cells may communicate via direct contact, without gap junctions (b) Cell-cell recognition proteins

In other cases, animal cells Communicate using localized chemical messengers (nearby communication) Paracrine signaling Synaptic signaling. diffusion Neuro- transmitter

Long-distance signaling Hormone travels in bloodstream to target cells Blood vessel Target Cells RESPOND Endocrine cell Plants and animals both use hormones for long-distance communication (signaling)

Earl Sutherland suggested that cells receiving [ chemical ] signals went through three processes: Reception (of a chem. signal) Transduction (change a signal from 1 form to another) Response

Simplified overview of cell signaling (communication) Receptor Relay molecules CYTOPLASM cellular response Reception Transduction Response Signal molecule Pathway!

The extracellular signal molecule is a type of Ligand. Intercellular proteins that bind to receptors triggering cellular responses Binding causes a conformational change in a receptor (a change in shape)

Intracellular transduction signals Signal molecules that are small or hydrophobic may freely diffuse across the cell membrane and directly initiate cellular metabolic responses

Example: Steroid hormones (hydrophobic) intracellular signalers Hormone (testosterone) Receptor protein DNA mRNA NUCLEUS CYTOPLASM New protein 1 passes through the plasma membrane. Activates a receptor 2 Complex enters nucleus activates a gene Protein synthesized

Receptors in the Plasma Membrane Three main types G-protein linked receptors Tyrosine kinases Ion receptor channels

G-protein-linked receptors Enzyme G-protein (switched off) Cellular response Activated! Activated Signal interacts with G proteins GDP GTP P Signal-binding site If ATP =… what does GTP =? G-protein (switched on)

Receptor tyrosine kinases Signal protein Tyrosines Helix Tyr Dimer Receptor tyrosine kinase proteins P Shapes match! Activated relay proteins responses Activated, unphosphorylated Fully activated 6 ATP 6 ADP

Here’s a more familiar communicator… Cellular response Gate open Gate closes Signal molecule (ligand) Gate closed Ions Ion channel receptors

Transduction : Cascading reactions (taking several steps) between receptor recognition to cell response These multistep pathways… amplify a signal Provide opportunities to refine regulation

Protein Phosphorylation and Dephosphorylation Each step that adds a phosphate group (remember?) Adds energy to a molecule, activating it Adds control and direction to the response to the original signal

In this process Protein kinases = enzymes that add a phosphate (energize) a molecule to another molecule Phosphatase enzymes then remove the phosphates, recirculating the molecule to be reused

Check it out on page 209! A phosphorylation cascade Signal molecule Active kinase1 Kinase 2 kinase3 kinase 1 2 3 Inactive protein Cellular response Receptor P ATP ADP PP Activated relay molecule i Phosphorylation cascade P  A relay molecule activates protein kinase 1. 1 Kinase + ATP’s P phos- Phorylation of protein kinase 3. 3 protein phosphatases (PP) Remove P gp, kinase is reused 5 Last phosphor. causes 4

Small molecules that act as 2nd messengers: 1. Cyclic AMP (cAMP) O –O N O P OH CH2 NH2 ATP Ch2 H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i

Many G-proteins trigger the formation of cAMP, a very impt 2ndary messenger… ATP GTP cAMP Protein kinase A response receptor G protein First messenger The 2nd messenger

Ca++ , another second messenger ATP CYTOSOL Ca2+ pump Nucleus Key High [Ca2+] Low [Ca2+]

response to a signal in the cytoplasm: Glucose (108 molecules) Glycogen Active glycogen phosphorylase (106) Inactive glycogen phosphorylase Active phosphorylase kinase (105) Inactive phosphorylase kinase Inactive protein kinase A Active protein kinase A (104) ATP Cyclic AMP (104) Active adenylyl cyclase (102) Inactive adenylyl cyclase Inactive G protein Active G protein (102 molecules) Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Response Reception Value of transduction: AMPLIFICATION

May activate transcription Other pathways May activate transcription Reception Transduction Response Gene P transcription factor DNA Phosphorylation cascade

Fine-Tuning of the Response Signal pathways with multiple steps… Can amplify the signal and contribute to the SENSITIVITY of the response