Cell Communication AP Biology Ms. Gaynor Chapter 11 Cell Communication AP Biology Ms. Gaynor

External signals  Cellular Responses Cells use Signal transduction pathways Convert signals OUTSIDE cell  cellular responses Similar in microbes and mammals, suggesting an early origin http://www.dnalc.org/resources/3d/cellsignals.html

Why do cells use chemical signals? To communicate without physical contact Communication distant can be small OR large Why study cell communcation? Allows humans to modify and change pathways, create drugs to help diseases, control diseases, agriculture production, fruit ripening, etc. What happens when cells fail to communicate properly? Abnormal development, diseases, cancer, death

Chemical Signals Signal molecules (ligand) Cells communicate through chemical messengers Signal molecules (ligand) growth factors neurotransmitters hormones (lipids) peptides (small proteins) Lipid soluble and insoluble

In local (short distance) signaling, cells may communicate via direct contact Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Both animals and plants have cell junctions that allow molecules Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Plasmodesmata between plant cells Gap junctions between animal cells Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

Bacteria & Cell-to-Cell Communcation Quorum sensing (short distance communication) Bacteria secrete chemical signal  helps bacteria coordinate behavior Regulation of gene expression in bacteria in response to external stimuli. Method used in response to population density

diffuses across synapse 2 types of Local signaling Usually, multicellular organisms communicate using local regulators Paracrine signaling. Secreting cell acts on nearby target cells by discharging molecules of a local regulator (i.e. growth factor) into extracellular fluid. 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 Target cell is stimulated 2 types of Local signaling Figure 11.4 A B

Long-distance signaling In long-distance signaling Both plants and animals use hormones Hormone travels in bloodstream to target cells Animal 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

3 Stages of Cell Signaling Earl W. Sutherland Discovered how the hormone epinephrine acts on cells http://highered.mcgraw-hill.com/olcweb/cgi/pluginpop.cgi?it=swf::535::535::/sites/dl/free/0072437316/120109/bio48.swf::Action%20of%20Epinephrine%20on%20a%20Liver%20Cell Sutherland suggested that cells receiving signals went through 3 processes Reception Transduction Response

Relay molecules in a signal transduction pathway Overview of cell signaling EXTRACELLULAR FLUID Receptor Signal molecule Relay molecules in a signal transduction pathway Plasma membrane CYTOPLASM Activation of cellular response Figure 11.5 Reception 1 Transduction 2 Response 3 http://www.biosolutions.info/2008/01/signal-transduction.html

STEP #1: Reception A signal molecule binds to a receptor protein  receptor changes shape Binding between signal (called ligand) & receptor protein is highly specific Changing shape  initiates transduction of the signal

Receptors 1st Type of Receptors Found in “target” cells 2 types/ locations 1. cell membrane (most abundant) called plasma membrane receptors 1st Type of Receptors

Plasma membrane receptors Chemical signal for these receptors can NOT pass THROUGH membrane…so it needs to be hydrophilic. WHY?

2nd type of Receptors 2. inside cell called intracellular receptors Found in cytoplasm or nucleus Chemical signal needs to pass THROUGH membrane…so it needs to be hydrophobic. WHY?

Intracellular receptors (con’t) Signal molecules that are small or hydrophobic WHY??? They can easily cross the plasma membrane Ex: lipid soluble steriod/hormones (such as testosterone)

Specific Examples of Receptors Involved in Cell Communication

New protein for MALE development Example #1: Intracellular receptor Ex: Steroid hormones Hormone (testosterone) EXTRACELLULAR FLUID Receptor protein DNA mRNA NUCLEUS CYTOPLASM Plasma membrane Hormone- receptor complex New protein for MALE development Figure 11.6 1 The steroid hormone testosterone passes through the plasma membrane. Testosterone binds to a receptor protein in the cytoplasm, activating it. 2 The hormone- receptor complex enters the nucleus and binds to specific genes. 3 The bound protein stimulates the transcription of the gene into mRNA. 4 The mRNA is translated into a specific protein. 5

Example #2, 3, 4: Cell Membrane Receptors There are 3 main types of membrane receptors G-protein-linked Tyrosine kinases Ion channel Names based on how they work!

1. G-protein-linked receptors G-Protein = short for guanine nucleotide (GTP)-binding proteins Ex: used in embryonic development, growth, smell, vision, over 60% of medications used today work by influencing G-protein pathways

G-protein-linked receptors All G-protein-linked receptors have similar structure regardless of the organism in which they are found Made of alpha-helices Signal-binding site on outside of cell G-protein-interacting site on inside of cell http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter9/signal_transduction_by_extracellular_receptors.html Ex: epinephrine http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html http://www.dnatube.com/view_video.php?viewkey=b4d3fbd5ba2ce59211f5

2. Tyrosine kinase Receptor Signal molecule Signal-binding sitea CYTOPLASM Tyrosines Signal molecule Helix in the Membrane Tyr Dimer Receptor tyrosine kinase proteins (inactive monomers) P Cellular response 1 Inactive relay proteins Activated relay proteins Cellular response 2 Activated tyrosine- kinase regions (unphosphorylated dimer) Fully activated receptor tyrosine-kinase (phosphorylated 6 ATP 6 ADP Figure 11.7 Ex: used cell growth and development, reproduction

Part of the Tyrosine Kinase receptor on cytoplasmic side serves as an enzyme Catalyzes transfer of Pi’s from ATP to amino acid Tyrosine on substrate http://www.wiley.com/college/fob/quiz/quiz21/21-15.html

Ex: used in nervous system Cellular response Gate open Gate close Ligand-gated ion channel receptor Plasma Membrane Signal molecule (ligand) Gate closed Ions 3. Ion channel receptors Ex: used in nervous system http://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter2/animation__receptors_linked_to_a_channel_protein.html

STEP #2: Transduction (converting the signal) Cascades of molecular interactions relay signals from receptors to target molecules in the cell Multistep pathways Can amplify a signal Provide more opportunities for coordination and regulation

Signal Transduction Pathways At each step in a pathway signal is transduced (converted) into a different form USUALLY a conformational change in a protein using… Protein Phosphorylation and Dephosphorylation

Phosphatase enzymes then remove the phosphates In this process A series of protein kinases add a phosphate to the next one in line, activating it VERY IMPORTANT ~2% of our genes Single cell has 100’s of different kinds of kinases (substrate specific) Phosphatase enzymes then remove the phosphates

A phosphorylation cascade: like a Pi relay!! Signal molecule Active protein kinase 1 2 3 Inactive protein kinase Cellular response Receptor P ATP ADP PP Activated relay molecule i Phosphorylation cascade P  A relay molecule activates protein kinase 1. 1 2 Active protein kinase 1 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 2 then catalyzes the phos- phorylation (and activation) of protein kinase 3. 3 Enzymes called protein phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. 5 Finally, active protein kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. 4 Figure 11.8

Small Molecules and Ions act as Second Messengers Are small, nonprotein, water-soluble molecules or ions Ex: cAMP (cyclic AMP), Ca2+, IP3 http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter9/second_messenger__camp.html

Cyclic AMP Cyclic AMP (cAMP) Is made from ATP by adenylyl cyclase (but cAMP is short lived!) Figure 11.9 O –O N O P OH CH2 NH2 ATP Ch2 H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i

Many G-proteins Cellular responses Trigger the formation of cAMP, which then acts as a second messenger in cellular pathways ATP GTP cAMP Protein kinase A Cellular responses G-protein-linked receptor Adenylyl cyclase G protein First messenger (signal molecule such as epinephrine) CAFFEINE BLOCKS cAMP  AMP BY PHOPHODIESTERASE SO cAMP LEVELS REMAIN HIGH Figure 11.10

Other Secondary Messagers… Inositol triphosphate (IP3) Triggers increase in calcium ions in the cytosol by inducing the release of Ca+2 from the ER Calcium (Ca+2) Ex: involved in muscle contractions

Figure 11.12 3 2 1 4 6 5 EXTRA- CELLULAR FLUID Signal molecule IP3 quickly diffuses through the cytosol and binds to an IP3– gated calcium channel in the ER membrane, causing it to open. 4 The calcium ions activate the next protein in one or more signaling pathways. 6 Calcium ions flow out of the ER (down their con- centration gradient), raising the Ca2+ level in the cytosol. 5 DAG functions as a second messenger in other pathways. Phospholipase C cleaves a plasma membrane phospholipid called PIP2 into DAG and IP3. A signal molecule binds to a receptor, leading to activation of phospholipase C. EXTRA- CELLULAR FLUID Signal molecule (first messenger) G protein G-protein-linked receptor Various proteins activated Endoplasmic reticulum (ER) Phospholipase C PIP2 IP3 (second messenger) DAG Cellular response (muscle contraction) GTP Ca2+ (second messenger) IP3-gated calcium channel Figure 11.12

Cell signaling leads to: STEP #3: Response Cell signaling leads to: regulation of cytoplasmic activities or nuclear activities Ex: transcription DNA  mRNA http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter9/intracellular_receptor_model.html

Cytoplasmic response to a signal Glucose-1-phosphate (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 Signal Amplification Each protein in a signaling pathway Amplifies (continues) signal by activating multiple copies of next component in the pathway Can be many or few proteins in cascasde Figure 11.13

Other pathways Regulate genes by activating transcription factors that turn genes on or off Reception Transduction Response mRNA NUCLEUS Gene P Active transcription factor Inactive DNA Phosphorylation cascade CYTOPLASM Receptor Growth factor Figure 11.14 http://highered.mcgraw-hill.com/sites/9834092339/student_view0/chapter9/how_intracellular_receptors_regulate_gene_transcription.html

Pathway branching and “cross-talk” Further help the cell coordinate incoming signals Response 1 Response 4 Response 5 Response 2 3 Signal molecule Cell A. Pathway leads to a single response Cell B. Pathway branches, leading to two responses Cell C. Cross-talk occurs between two pathways Cell D. Different receptor leads to a different response Activation or inhibition Receptor Relay molecules Figure 11.15

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Can increase the signal transduction efficiency Signal molecule Receptor Scaffolding protein Three different protein kinases Plasma membrane Figure 11.16

Termination of the Signal Signal response is terminated quickly By the reversal of ligand binding INACTIVE- TURNED “OFF” ACTIVE- TURNED “ON”

When things go wrong… Diabetes Heart disease Neurological or autoimmune disorders Cancer Death (ex: from neurotoxins, poisons, pesticides)

Great tutorial to use to study… http://www.biology.arizona.edu/CELL_BIO/problem_sets/signaling/04q.html