Signal Transduction Pathways Cell Communication Signal Transduction Pathways

Local Signaling Cells in a multicellular organism communicate by chemical messengers Animal and plant cells have cell junctions that directly connect the cytoplasm of adjacent cells In local signaling, animal cells may communicate by direct contact, or cell-cell recognition Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Gap junctions between animal cells Plasmodesmata between plant cells Fig. 11-4 Plasma membranes Gap junctions between animal cells Plasmodesmata between plant cells (a) Cell junctions Figure 11.4 Communication by direct contact between cells (b) Cell-cell recognition

(a) Paracrine signaling (b) Synaptic signaling Fig. 11-5ab Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secreting cell Secretory vesicle Figure 11.5 Local and long-distance cell communication in animals Local regulator diffuses through extracellular fluid Target cell is stimulated (a) Paracrine signaling (b) Synaptic signaling

Long-distance signaling In long-distance signaling, animals and plants use chemical messengers called hormones. Hormones are chemicals made in one area of the body that are delivered to other areas.

Long-distance signaling Fig. 11-5c Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Figure 11.5 Local and long-distance cell communication in animals Target cell (c) Hormonal signaling

What are Signal transduction pathways? A signal transduction pathway is a series of steps by which a signal on a cell’s surface is converted into a specific cellular response. In general there are 3 steps: 1) Reception 2) Transduction 3) Response

Plasma membrane 1 Reception Receptor Signaling molecule 1 Fig. 11-6-1 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception Receptor Figure 11.6 Overview of cell signaling Signaling molecule

Plasma membrane 1 Reception Transduction Receptor Signaling molecule 1 Fig. 11-6-2 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 1 Reception 2 Transduction Receptor Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling Signaling molecule

Plasma membrane 1 Reception Transduction Response Receptor Activation Fig. 11-6-3 EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Figure 11.6 Overview of cell signaling Signaling molecule

Step 1: reception In Step 1, Reception: a signaling molecule binds to a receptor protein, causing it to change shape. Ligand: the signaling molecule Receptor: a molecule (usually a protein) on the surface of a cell that recognizes and binds to a ligand The binding between a ligand and its’ receptor is highly specific.

Receptors in the Plasma Membrane Most water-soluble signal molecules bind to specific sites on receptor proteins in the plasma membrane Examples of membrane receptors: G protein-coupled receptors Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

G-Protein-Coupled Receptors A G protein-coupled receptor is a plasma membrane receptor that works with the help of a G protein The G protein acts as an on/off switch: If GDP is bound to the G protein, the G protein is inactive Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-7b Plasma membrane G protein-coupled receptor Inactive enzyme Activated receptor Signaling molecule GDP G protein (inactive) Enzyme GDP GTP CYTOPLASM 1 2 Activated enzyme Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2 GTP GDP P i Cellular response 3 4

Ligand-gated Ion Channel Receptor A ligand-gated ion channel receptor acts as a gate when the receptor changes shape When a signal molecule binds as a ligand to the receptor, the gate allows specific ions, such as Na+ or Ca2+, through a channel in the receptor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

1 Signaling molecule (ligand) Gate closed Ions Plasma membrane Fig. 11-7d 1 Signaling molecule (ligand) Gate closed Ions Plasma membrane Ligand-gated ion channel receptor 2 Gate open Cellular response Figure 11.7 Membrane receptors—ion channel receptors 3 Gate closed

Step 2: Transduction In Step 2, Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Transduction: the conversion of a signal outside the cell to a form that can bring about a specific cellular response.

Signal Transduction Pathways Signal transduction usually involves multiple steps, called a signal cascade. Multi-step pathways (signaling cascades) can amplify a signal; even just a few molecules can cause a large cell response. Advantage: multi-step pathways can provide for more ways to coordinate and regulate the response. Multi-step pathways also allow for more specificity in the response.

Phosphorylation cascade Fig. 11-9 Signaling molecule 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 Figure 11.9 A phosphorylation cascade 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

Second Messengers The extracellular signal molecule that binds to the receptor is a pathway’s “first messenger” Second messengers are small, non-protein, water-soluble molecules or ions that spread throughout a cell by diffusion Second messengers participate in pathways initiated by G protein-coupled receptors Cyclic AMP and calcium ions are common second messengers Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Cyclic AMP Cyclic AMP (cAMP) is one of the most widely used second messengers Adenylyl cyclase, an enzyme in the plasma membrane, converts ATP to cAMP in response to an extracellular signal Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Conversion of ATP to cAMP to AMP Fig. 11-10 Conversion of ATP to cAMP to AMP Adenylyl cyclase Phosphodiesterase Pyrophosphate P P i ATP cAMP AMP Figure 11.10 Cyclic AMP

Triggering the making of cAMP Many signal molecules trigger formation of cAMP cAMP usually activates protein kinase A, which phosphorylates various other proteins Further regulation of cell metabolism is provided by G-protein systems that inhibit adenylyl cyclase. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

First messenger Adenylyl cyclase G protein GTP G protein-coupled Fig. 11-11 First messenger Adenylyl cyclase G protein G protein-coupled receptor GTP ATP Second messenger cAMP Figure 11.11 cAMP as second messenger in a G-protein-signaling pathway Protein kinase A Cellular responses

Calcium Ions Calcium ions (Ca2+) act as a second messenger in many pathways Calcium is an important second messenger because cells can regulate its concentration Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Fig. 11-12 EXTRACELLULAR FLUID Plasma membrane Ca2+ pump ATP Mitochondrion Nucleus CYTOSOL Ca2+ pump Endoplasmic reticulum (ER) Figure 11.12 The maintenance of calcium ion concentrations in an animal cell Ca2+ pump ATP Key High [Ca2+] Low [Ca2+]

Step 3: Response In Step 3, Response: Cell signaling leads to regulation of transcription or a change in the cell’s activities. This is sometimes called the “output response”. Transcription: One of the processes involved in genes that determines which proteins will be made in the cell Other cell signaling pathways may regulate the action of an enzyme.

Growth factor Reception Receptor Phosphorylation cascade Transduction Fig. 11-14 Growth factor Reception Receptor Phosphorylation cascade Transduction CYTOPLASM Inactive transcription factor Active transcription factor Figure 11.14 Nuclear responses to a signal: the activation of a specific gene by a growth factor Response P DNA Gene NUCLEUS mRNA

The stimulation of glycogen breakdown by epinephrine: Fig. 11-15 Reception Binding of epinephrine to G protein-coupled receptor (1 molecule) Transduction Inactive G protein The stimulation of glycogen breakdown by epinephrine: Active G protein (102 molecules) This is an example of a phosphory- lation cascade Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A Active protein kinase A (104) Figure 11.15 Cytoplasmic response to a signal: the stimulation of glycogen breakdown by epinephrine Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1-phosphate (108 molecules)

Changes in signal transduction pathways Changes in signal transduction pathways can alter cellular response. For Example: Conditions where signal transduction is blocked or defective can be deleterious (bad), preventative, or prophylactic (good).

What would happen if one of the relay molecules was defective? Fig. 11-UN1 What would happen if one of the relay molecules was defective? 1 Reception 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules Signaling molecule

Question: how does caffeine work on the brain? Caffeine has many effects on the body, but the most noticeable is that it keeps us awake. The caffeine molecule is large and polar, so it doesn’t diffuse easily across the cell membrane. Instead it binds to receptors on the surfaces of nerve cells in the brain.

adenosine Adenosine (a nucleoside) accumulates in the brain when a person is under stress or has prolonged mental activity. When it binds to a specific receptor in the brain, adenosine sets in motion a signal transduction pathway that results in reduced brain activity, which usually means drowsiness.

Caffeine and adenosine Caffeine has a 3-dimensional structure similar to adenosine and is able to bind to the adenosine receptor. Because its binding does not activate the receptor, caffeine functions as a antagonist of adenosine signaling, with the result that the brain stays active. Caffeine Adenosine

caffeine Because caffeine has bound to the adenosine receptor, the adenosine has little effect, and the person stays awake. The binding of caffeine to the adenosine receptor, however, is a reversible reaction. In time, the caffeine molecules come off the adenosine receptors in the brain, allowing adenosine to bind once again.

Additional effects of caffeine In addition to competing with adenosine for a membrane receptor, caffeine blocks the enzyme cAMP phosphodiesterase. This enzyme breaks down cAMP, which is a second messenger in the pathway that turns glycogen into sugar which is then released into the bloodstream. Can you see how caffeine increases the “fight or flight” response?