Cell Communication

The “Cellular Internet” Biologists have discovered some universal mechanisms of cellular regulation that involve cell-to-cell communication. External signals are converted into responses within the cell

Evolution of Cell Signaling Yeast cells Identify their mates by cell signaling  factor Receptor 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 Yeast cell, mating type a mating type   a/ a Figure 11.2

Methods used by Cells to Communicate Cell-Cell communication Cell Signaling using chemical messengers Local signaling over short distances Cell-Cell Recognition Local regulators Paracrine (growth factors) Synaptic (neurotransmitters) Long distance signaling Hormones

Cell-Cell Communication 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 Figure 11.3 (a) Cell junctions. Both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes.

Cell-Cell Communication Animal cells use gap junctions to send signals Cells must be in direct contact Protein channels connecting two adjoining cells Gap junctions between animal cells

Cell-Cell Communication Plant cells use plasmodesmata to send signals Cells must be in direct contact Gaps in the cell wall connecting the two adjoining cells together Plasmodesmata between plant cells

Local Signaling: Cell-Cell Recognition In local signaling, animal cells may communicate via direct contact Membrane bound cell surface molecules Glycoproteins Glyolipids Figure 11.3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Local Signaling: Local Regulators In other cases, animal cells Communicate using local regulators Only work over a short distance (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: Hormones In long-distance signaling Both plants and animals use hormones 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

Long-Distance Signaling Nervous System in Animals Electrical signals through neurons Endocrine System in Animals Uses hormones to transmit messages over long distances Plants also use hormones Some transported through vascular system Others are released into the air

The Three Stages of Cell Signaling Earl W. Sutherland (1971) Discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response Called Signal transduction pathways Convert signals on a cell’s surface into cellular responses Are similar in microbes and mammals, suggesting an early origin

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

Three Stages of Cell Signaling EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception The receptor and signaling molecules fit together (lock and key model, induced fit model, just like enzymes!) Receptor Signaling molecule Signaling molecule binds to the receptor protein

Three Stages of Cell Signaling EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception 2 Transduction Receptor 2nd Messenger! Relay molecules in a signal transduction pathway Signaling molecule The signal is converted into a form that can produce a cellular response

Three Stages of Cell Signaling EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Can be catalysis, activation of a gene, triggering apoptosis, almost anything! Signaling molecule The transduced signal triggers a cellular response

Signal Transduction Animation http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&A http://www.wiley.com/legacy/college/boyer/0470003790/animations/signal_transduction/signal_transduction.htm

There are three most common types of membrane receptor proteins. G-protein coupled receptors Receptor tyrosine-kinases Ion channel receptors

The G-protein is a common membrane receptor. 1. Reception A signal molecule, a ligand, binds to a receptor protein in a lock and key fashion, causing the receptor to change shape. Most receptor proteins are in the cell membrane but some are inside the cell. The G-protein is a common membrane receptor.

G-Protein Coupled Receptors are often involved in diseases such as bacterial infections. G-Protein Receptors Inactive enzyme Plasma membrane G protein-coupled receptor Activated receptor Signaling molecule Enzyme GDP 1 2 GDP GTP CYTOPLASM G protein (inactive) Activated enzyme i GTP GDP P 3 4 Cellular response

Receptor tyrosine kinases Signal molecule Signal-binding site 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

Ion Channel Receptors Very important in the nervous system Gate closed 1 Ions Signaling molecule (ligand) Very important in the nervous system Signal triggers the opening of an ion channel depolarization Triggered by neurotransmitters Ligand-gated ion channel receptor Plasma membrane 2 Gate open Cellular response 3 Gate closed

2. Transduction Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Multistep pathways Can amplify a signal (Amplifies the signal by activating multiple copies of the next component in the pathway) Provide more opportunities for coordination and regulation At each step in a pathway, the signal is transduced into a different form, commonly a conformational change in a protein.

Phosphorylation cascade Fig. 11-9 Signaling molecule Transduction: A Phosphorylation Cascade Receptor Activated relay molecule Inactive protein kinase 1 Active protein kinase 1 Inactive protein kinase 2 ATP Phosphorylation cascade ADP Active protein kinase 2 P PP P i Inactive protein kinase 3 ATP ADP Active protein kinase 3 P PP P i Inactive protein ATP ADP P Active protein Cellular response PP P i

Protein Phosphorylation and Dephosphorylation Many signal pathways Include phosphorylation cascades In this process, a series of protein kinases add a phosphate to the next one in line, activating it Phosphatase enzymes then remove the phosphates

A phosphorylation cascade 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

About 1% of our genes are thought to code for kinases. The transduction stage of signaling is often a multistep process that amplifies the signal. About 1% of our genes are thought to code for kinases. http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&C

Small Molecules and Ions as Second Messengers Secondary messengers Are small, nonprotein, water-soluble molecules or ions that act as secondary messengers.

Cyclic AMP Many G-proteins 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) Figure 11.10

Cyclic AMP Cyclic AMP (cAMP) Is made from ATP O –O N O P OH CH2 NH2 H2O HO Adenylyl cyclase Phoshodiesterase Pyrophosphate Cyclic AMP AMP i

Transduction in a G-protein pathway Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP Second messenger cAMP Transduction in a G-protein pathway Protein kinase A Cellular responses

Calcium ions and Inositol Triphosphate (IP3) Calcium, when released into the cytosol of a cell acts as a second messenger in many different pathways Calcium is an important second messenger because cells are able to regulate its concentration in the cytosol EXTRACELLULAR FLUID Plasma membrane ATP CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Nucleus Mitochondrion Key High [Ca2+] Low [Ca2+] Other second messengers such as inositol triphosphate and diacylglycerol can trigger an increase in calcium in the cytosol

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 GTP Ca2+ (second messenger) IP3-gated calcium channel Figure 11.12

3. Response Many possible outcomes Growth factor 3. Response Receptor Reception Many possible outcomes This example shows a transcription response Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Response P DNA Gene NUCLEUS mRNA

Specificity of the signal Signaling molecule Specificity of the signal The same signal molecule can trigger different responses Many responses can come from one signal! Receptor Relay molecules Response 1 Response 2 Response 3 Cell A. Pathway leads to a single response. Cell B. Pathway branches, leading to two responses.

The signal can also trigger an activator or inhibitor The signal can also trigger multiple receptors and different responses Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

Response- cell signaling leads to regulation of transcription (turn genes on or off) or cytoplasmic activities.

Testosterone acts as a transcription factor. Long-distance Signaling Intracellular signaling includes hormones that are hydrophobic and can cross the cell membrane. Once inside the cell, the hormone attaches to a protein that takes it into the nucleus where transcription can be stimulated. Testosterone acts as a transcription factor.

Steroid hormones Bind to intracellular receptors Figure 11.6 1 2 3 4 5 (testosterone) EXTRACELLULAR FLUID Receptor protein DNA mRNA NUCLEUS CYTOPLASM Plasma membrane Hormone- receptor complex New protein 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

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

Any Questions?? Can You Hear Me Now?

Two systems control all physiological processes 1. Nervous System – neurosecretory glands in endocrine tissues secrete hormones. 2. Endocrine System

Human Endocrine System

Major Vertebrate Endocrine Glands Their Hormones (Hypothalamus–Parathyroid glands) 45

Each system affects the output of the other Each system affects the output of the other. Feed back is another common feature. Neurosecretory cells in endocrine organs and tissues secrete hormones. These hormones are excreted into the circulatory system. 47

Stress and the Adrenal Gland 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

Figure 45.4 One chemical signal, different effects 49

http://bcs.whfreeman.com/thelifewire/content/chp42/4202003.html 50

http://vcell.ndsu.nodak.edu/animations/regulatedsecretion/movie.htm 51

Cellular Communication Review Denise Green

REVIEW: Signal-transduction pathway Definition: Signal on a cell’s surface is converted into a specific cellular response Local signaling (short distance): √ Paracrine (growth factors) √ Synaptic (neurotransmitters) Long distance: hormones

Stages of cell signaling Sutherland (‘71) Glycogen depolymerization by epinephrine 3 steps: •Reception: target cell detection •Transduction: single-step or series of changes •Response: triggering of a specific cellular response

G-protein-linked receptors Plasma Membrane Enzyme G-protein (inactive) CYTOPLASM Cellular response Activated enzyme Activated Receptor Signal molecule Inctivate Segment that interacts with G proteins GDP GTP P i Signal-binding site Figure 11.7

Protein phosphorylation Protein activity regulation Adding phosphate from ATP to a protein (activates proteins) Enzyme: protein kinases (1% of all our genes) Example: cell reproduction Reversal enzyme: protein phosphatases

Second messengers Non-protein signaling pathway Example: cyclic AMP (cAMP) Ex: Glycogen breakdown with epinephrine Enzyme: adenylyl cyclase G-protein-linked receptor in membrane (guanosine di- or tri- phosphate)

Cellular responses to signals Cytoplasmic activity regulation Cell metabolism regulation Nuclear transcription regulation

2010 Free Response Question

The three stage of cellular signaling: Reception, Transduction, and Response. http://media.pearsoncmg.com/bc/bc_campbell_biology_7/media/interactivemedia/activities/load.html?11&A