Cell Communication

Cell Communication: The Cellular Internet Cell-to-cell communication is essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular regulation The combined effects of multiple signals determine cell response For example, the dilation of blood vessels is controlled by multiple molecules Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Evolution of Cell Signaling 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 Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Evolution of Cell Signaling Pathway similarities suggest that ancestral signaling molecules evolved in prokaryotes and were modified later in eukaryotes The concentration of signaling molecules allows bacteria to detect population density Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Local and Long-Distance 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

Local vs. Long Distance Signaling In many other cases, animal cells communicate using local regulators, messenger molecules that travel only short distances In long-distance signaling, plants and animals use chemicals called hormones Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

(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 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

The Three Stages of Cell Signaling: Earl W. Sutherland discovered how the hormone epinephrine acts on cells Sutherland suggested that cells receiving signals went through three processes: Reception Transduction Response Animation: Overview of Cell Signaling Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

Most signal receptors are plasma membrane proteins Reception: A signal molecule binds to a receptor protein, causing it to change shape The binding between a signal molecule (ligand) and receptor is highly specific A shape change in a receptor is often the initial transduction of the signal Most signal receptors are plasma membrane proteins Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Membrane Receptors There are three main types of membrane receptors: G protein-coupled receptors Receptor tyrosine kinases Ion channel receptors Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

1. G Protein-Coupled Receptor Membrane receptor Works with the help of a G protein, a protein that binds the energy rich molecule GTP. 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

Signaling-molecule binding site Fig. 11-7a Signaling-molecule binding site Figure 11.7 Membrane receptors—G protein-coupled receptors, part 1 Segment that interacts with G proteins G protein-coupled receptor

Figure 11.7 Membrane receptors—G protein-coupled receptors, part 2 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

2. Receptor Tyrosine Kinases membrane receptors Have enzymatic activity attach phosphates to tyrosines Can trigger multiple signal transduction pathways at once, therefore can help cell regulate and co-ordinate cell growth and reproduction Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fully activated receptor tyrosine kinase Fig. 11-7c Signaling molecule (ligand) Ligand-binding site Signaling molecule  Helix Tyr Tyr Tyrosines Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Tyr Receptor tyrosine kinase proteins Dimer CYTOPLASM 1 2 Activated relay proteins Figure 11.7 Membrane receptors—receptor tyrosine kinases Cellular response 1 Tyr Tyr P Tyr Tyr P Tyr Tyr P P Tyr Tyr P Tyr Tyr P Tyr Tyr P P Cellular response 2 Tyr Tyr P Tyr Tyr P Tyr P Tyr P 6 ATP 6 ADP Activated tyrosine kinase regions Fully activated receptor tyrosine kinase Inactive relay proteins 3 4

3. Ligand-gated ion channel 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

Intracellular Receptors Some receptor proteins are intracellular, found in the cytoplasm or nucleus of target cells Small or hydrophobic chemical messengers can readily cross the membrane and activate receptors Examples of hydrophobic messengers are the steroid and thyroid hormones of animals An activated hormone-receptor complex can act as a transcription factor, turning on specific genes Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Hormone (testosterone) Plasma membrane Receptor protein Hormone- Fig. 11-8-5 Hormone (testosterone) EXTRACELLULAR FLUID Plasma membrane Receptor protein Hormone- receptor complex DNA Figure 11.8 Steroid hormone interacting with an intracellular receptor mRNA NUCLEUS New protein CYTOPLASM

Usually involves multiple steps Transduction: Cascades of molecular interactions relay signals from receptors to target molecules in the cell Usually involves multiple steps Can amplify a signal: A few molecules can produce a large cellular response Provide more opportunities for coordination and regulation of the cellular response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Signal Transduction Pathways The molecules that relay a signal from receptor to response are mostly proteins. Like falling dominoes, the receptor activates another protein, which activates another, and so on, until the protein producing the response is activated. At each step, the signal is transduced into a different form, usually a shape change in a protein. Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Protein Phosphorylation and Dephosphorylation In many pathways, the signal is transmitted by a cascade of protein phosphorylations, carried out by protein kinases, which transfer phosphates from ATP to protein. Protein phosphatases remove the phosphates from proteins, a process called dephosphorylation This phosphorylation and dephosphorylation system acts as a molecular switch, turning activities on and off Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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, nonprotein, water-soluble molecules or ions that spread throughout a cell by diffusion Cyclic AMP and calcium ions are common second messengers Adenyl 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

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

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+]

The final activated molecule may function as a transcription factor Response: Cell signaling leads to regulation of transcription or cytoplasmic activities Ultimately, a signal transduction pathway leads to regulation of one or more cellular activities The response may occur in the cytoplasm or may involve action in the nucleus Many signaling pathways regulate the synthesis of enzymes or other proteins, usually by turning genes on or off in the nucleus The final activated molecule may function as a transcription factor Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

Fine-Tuning of the Response Multistep pathways have two important benefits: Amplifying the signal (and thus the response) Contributing to the specificity of the response Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Fig. 11-17 Figure 11.17 The specificity of cell signaling Signaling molecule 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. Figure 11.17 The specificity of cell signaling Activation or inhibition Response 4 Response 5 Cell C. Cross-talk occurs between two pathways. Cell D. Different receptor leads to a different response.

Signaling Efficiency: Scaffolding Proteins and Signaling Complexes Scaffolding proteins are large relay proteins to which other relay proteins are attached Scaffolding proteins can increase the signal transduction efficiency by grouping together different proteins involved in the same pathway Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Signaling Plasma molecule membrane Receptor Three different protein Fig. 11-18 Signaling molecule Plasma membrane Receptor Three different protein kinases Figure 11.18 A scaffolding protein Scaffolding protein

Termination of the Signal When signal molecules leave the receptor, the receptor reverts to its inactive state Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Apoptosis Programmed or controlled cell death Integrates multiple cell-signaling pathways Cell is chopped and packaged into vesicles that are digested by scavenger cells Prevents enzymes from leaking out of a dying cell and damaging neighboring cells Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Apoptosis in the Soil Worm Caenorhabditis elegans Apoptosis is important in shaping an organism during embryonic development The role of apoptosis in embryonic development was first studied in Caenorhabditis elegans Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

Signals That Trigger Apoptosis Caspases are the main proteases (enzymes that cut up proteins) that carry out apoptosis Apoptosis can be triggered by: An extracellular death-signaling ligand DNA damage in the nucleus Protein misfolding in the endoplasmic reticulum Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings