Warm-Up Why do you communicate? How do you communicate? How do you think cells communicate? Do you think bacteria can communicate? Explain.

Warm-Up Compare the structure & function of these receptor proteins: GPCR, tyrosine kinase and ligand-gated ion channels. What is a second messenger? What are some examples of these molecules? What are the possible responses to signal transduction in a cell?

POGIL: Cell Communication Table 1 Table 2 Table 3 Table 6 Station 7 Station 8 Group 9 Yafeit Misah Harley Will Pearson Julia Emmie Marco Hoyt Benjamin Mina Hannah George Natalie Everette (Caitlin) Duwe Detlow Elle Langley W. Shelley Sidra Biniyam (Nayana) Josue Sarah DJ Trinity

Cell Communication CHAPTER 11

Do bacteria communicate? Bonnie Bassler on How Bacteria “Talk”

Video Questions: Why are scientists studying how bacteria (and not just human cells) communicate? What is quorum sensing? Describe how Vibrio fischeri use quorum sensing in squid. According to Bonnie Bassler (Princeton University), what are scientists hoping to use as the next class of antibiotics?

Cell Signaling Animal cells communicate by: Direct contact (gap junctions) Secreting local regulators (growth factors, neurotransmitters) Long distance (hormones)

Local/short distance; neurotransmitters move across a synapse Long distance; hormones travel through bloodstream

3 Stages of Cell Signaling: Reception: Detection of a signal molecule (ligand) coming from outside the cell Transduction: Convert signal to a form that can bring about a cellular response (often involves amplification) Response: Cellular response to the signal molecule

Reception Protein Ligand

Transduction Amplification

Response If in the nucleus, the response activates genes If in cytoplasm, activates enzymes/proteins

1. Reception Binding between signal molecule (ligand) + receptor is highly specific. Types of Receptors: Plasma membrane receptor Bind water-soluble ligands Intracellular receptors (cytoplasm, nucleus) hydrophobic or small ligands Eg. testosterone or nitric oxide (NO) Ligand binds to receptor protein  protein changes SHAPE  initiates transduction signal Complementary shapes (just like enzymes and substrates!) Allow for facilitated diffusion

Plasma Membrane Receptors Cell Surface Transmembrane Proteins G-Protein Coupled Receptor (GPCR) Tyrosine Kinases Ligand-Gated Ion Channels Very widespread in animals/humans Work with the help of a G protein – binds to GTP (energy molecule similar to ATP)

G-Protein-Coupled Receptor

G-Protein-Coupled Receptor G protein is a molecular switch. Inactive/off when GDP is bound Active/on when GTP is bound G proteins work together with an a receptor (GPCR) G proteins work together with an enzyme (or other protein)

G-Protein-Coupled Receptor Signaling molecule (ligand) binds to cytoplasm side of GPCR Receptor is activated and changes shape. Cytoplasm side of the receptor then binds inactive G protein, causing GTP to displace GDP This activates the G protein

G-Protein-Coupled Receptor Activated G protein leaves the receptor and moves down the membrane to an enzyme Signaling molecule can bind/unbind many times Activated enzyme changes shape and triggers next step in cell response.

G-Protein-Coupled Receptor Changes in G protein and enzyme are temporary. G protein also acts a GTPase enzyme (hyrdolyzes bound GTP to GDP) Everything resets and G protein can be used again.

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Very widespread in animals/humans Work with the help of a G protein – binds to GTP (energy molecule similar to ATP) 7 transmembrane segments in membrane G protein + GTP activates enzyme  cell response

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Very widespread in animals/humans Receptors that act as enzymes Work with the help of a G protein – binds to GTP (energy molecule similar to ATP) Transfers P group from ATP to the amino acid tyrosine 7 transmembrane segments in membrane G protein + GTP activates enzyme  cell response

Receptor Tyrosine Kinase

Receptor Tyrosine Kinase Signal molecules (ligands) binds to both monomers Monomers come together and form a dimer (=dimerization)

Receptor Tyrosine Kinase Each tyrosine kinase adds a phosphate from ATP to the tyrosines on the tails

Receptor Tyrosine Kinase Relay proteins inside the cell bind to specific phosphorylated tyrosine, undergoes a shape change, and then triggers a transduction pathway leading to a cellular response.

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Very widespread in animals/humans Receptors that act as enzymes Work with the help of a G protein – binds to GTP (energy molecule similar to ATP) Transfers P group from ATP to the amino acid tyrosine 7 transmembrane segments in membrane Activate multiple cellular responses at once G protein + GTP activates enzyme  cell response Abnormal RTKs are associated with many cancers

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Very widespread in animals/humans Receptors that act as enzymes Region on receptor changes shape and acts like a “gate” when signal molecule binds Work with the help of a G protein – binds to GTP (energy molecule similar to ATP) Transfers P group from ATP to the amino acid tyrosine Gates may open or close to regulate flow of specific ions (Ca2+, Na+) 7 transmembrane segments in membrane Activate multiple cellular responses at once G protein + GTP activates enzyme  cell response Abnormal RTKs are associated with many cancers

Ligand-Gated Ion Channel Ligand binds to receptor (closed)  shape change  gate opens The gate closes when the ligand dissociates Ions flow into the cell through open gate; activates cell in some way

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Very widespread in animals/humans Receptors that act as enzymes Region on receptor changes shape and acts like a “gate” when signal molecule binds Work with the help of a G protein – binds to GTP (energy molecule similar to ATP) Transfers P group from ATP to the amino acid tyrosine Gates may open or close to regulate flow of specific ions (Ca2+, Na+) 7 transmembrane segments in membrane Activate multiple cellular responses at once Important in nervous system G protein + GTP activates enzyme  cell response Abnormal RTKs are associated with many cancers Some gated ion channels are controlled by electrical signals instead of ligands. These are voltage-gated ion channels

POGIL: Signal Transduction Pathways

The Fight or Flight Response http://learn.genetics.utah.edu/content/cells/cellcom/

Bozeman Science: Signal Transmission and Gene Expression Complete the review sheet while you watch

2. Transduction Cascades of molecular interactions relay signals from receptors to target molecules Usually involve Protein kinases: enzymes that phosphorylate (transfer a phosphate group from ATP to a protein) and activate proteins at next level (turn signal on) Protein phosphatases: enzymes that remove phosphate groups and inactivate protein kinases (can turn signal off) Phosphorylation cascade: helps to enhance and amplify signal to allow a greater cellular response

Second Messengers small, nonprotein molecules/ions that can relay signal inside cell Eg. cyclic AMP (cAMP), calcium ions (Ca2+), inositol triphosphate (IP3) Once activated, initiate a phosphorylation cascade

cAMP cAMP = cyclic adenosine monophosphate GPCR  adenylyl cyclase (convert ATP  cAMP)  activate protein kinase A

3. Response Regulate protein synthesis by turning on/off genes in nucleus (gene expression) Regulate activity of proteins (including enzymes) in cytoplasm

Bozeman Science Signal Transduction Pathways Complete the review sheet while you watch

Signal Transduction Pathway Problems/Defects: Examples: Diabetes Cholera Autoimmune disease Cancer Neurotoxins, poisons, pesticides Drugs (anesthetics, antihistamines, blood pressure meds)

Cholera 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 Disease acquired by drinking contaminated water (w/human feces) Bacteria (Vibrio cholerae) colonizes lining of small intestine and produces toxin

Viagra Used as treatment for erectile dysfunction Inhibits hydrolysis of cGMP  GMP Prolongs signal to relax smooth muscle in artery walls; increase blood flow to penis

Viagra inhibits cGMP breakdown

Apoptosis = cell suicide Cell is dismantled and digested Triggered by signals that activate cascade of “suicide” proteins (caspase) Why? Protect neighboring cells from damage Animal development & maintenance May be involved in some diseases (Parkinson’s, Alzheimer’s)

Apoptosis of a human white blood cell Figure 11.19 Apoptosis of human white blood cells Left: Normal WBC Right: WBC undergoing apoptosis – shrinking and forming lobes (“blebs”)

Effect of apoptosis during paw development in the mouse Figure 11.21 Effect of apoptosis during paw development in the mouse

Bozeman Science Effects of Changes in Pathways Complete the review sheet while you watch

Dropping Signals Complete the online exploration and fill in the chart. Read the article about Viagra and annotate.