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?

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)

Cell-to-Cell Communications Cell junctions directly connect the cytoplasm of adjacent cells Ex: cardiac cells for rhythmicity; plamodesmata between plant cells Surface receptors can give/send information Ex: specific immune response VIDEO Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells

diffuses across synapse Local Signaling VIDEO Adjacent cells are signaled. Chemical messengers released Ex: Neurotransmitters via neurons (a) Paracrine signaling. A secreting cell acts on nearby target cells by discharging molecules of a local regulator (a growth factor, for example) into the extracellular fluid. (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell. Local regulator diffuses through extracellular fluid Target cell Secretory vesicle Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse is stimulated Local signaling

Long Distance Signaling Use of hormones Both plants and animals use hormones (e.g. Insulin) Can affect many cells in Other parts of the body Protein or Steroid types Hormone travels in bloodstream to target cells (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all body cells. Long-distance signaling Blood vessel Target cell Endocrine cell Figure 11.4 C

How Does it Work? Signal Transduction Pathways Convert signals on a cell’s surface into cellular responses Are similar in microbes and mammals, suggesting an early origin

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 Response: Cellular response to the signal molecule

Reception

Transduction

Response

1. Reception Binding between signal molecule (ligand) + receptor is highly specific. Types of Receptors: Plasma membrane receptor 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

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels

G-Protein-Coupled Receptor

G-Protein-Coupled Receptor Very Common Results in a single pathway response

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels 7 transmembrane segments in membrane G protein + GTP activates enzyme  cell response

Receptor Tyrosine Kinase Multiple Pathway Response

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Attaches (P) to tyrosine Activate multiple cellular responses at once

Ligand-Gated Ion Channel When ligand binds, channel can open or close Ex: neurotransmitters bind as ligands for Na+ ion channels

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Signal on receptor changes shape Regulate flow of specific ions (Ca2+, Na+)

2. Transduction Cascades of molecular interactions relay signals from receptors  target molecules Protein kinase: enzyme that phosphorylates and activates proteins at next level Phosphorylation cascade: enhance and amplify signal

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

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 in cytoplasm

An Example of Cell Communication http://learn.genetics.utah.edu/content/begin/cells/cellcom/

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