Chapter 11 CELL COMMUNICATION Celltocell communication Is absolutely

Chapter 11 CELL COMMUNICATION

Cell-to-cell communication Is absolutely essential for multicellular organisms Biologists have discovered some universal mechanisms of cellular regulation cells most often communicate with other cells by chemical signals

Concept 11. 1: External signals are converted into responses within the cell

Signal transduction pathways Convert signals on a cell’s surface into cellular responses Are similar in microbes and mammals, suggesting an early origin Scientists think signaling mechanisms 1 st evolved in ancient prokaryotes & unicellular eukaryotes then adopted for new uses by their multicellular descendants

Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment. Correct and appropriate signal transduction processes are generally under strong selective pressure. Single-Celled Organisms Multicellular Organisms Environmental response Coordination of Activities Quorum sensing How epinephrine is linked to glycogen breakdown

Communication Among Bacteria quorum sensing: bacteria release small molecules detected by like bacteria: gives them a “sense” of local density of cells allows them to coordinate activities only productive when performed by given # in synchrony ex: forming a biofilm: aggregation of bacteria adhered to a surface: slime on fallen leaves or on your teeth in the morning (they cause cavities)

Biofilm Development

Cells can communicate with each other through direct contact with other cells or from a distance via chemical signaling.

Direct Contact Communication Animal and plant cells Have cell junctions that directly connect the cytoplasm of adjacent cells Plasma membranes Gap junctions between animal cells Plasmodesmata between plant 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.

Direct Contact Communication In local signaling, animal cells May communicate via direct contact Figure 11. 3 (b) Cell-cell recognition. Two cells in an animal may communicate by interaction between molecules protruding from their surfaces.

Local Signaling Cells in a multicellular organism Communicate via chemical messengers Paracrine signaling local signaling cells send messages to local regulator cells synaptic signaling action potential travels thru cell membrane of neuron triggering exocytosis of neurotransmitter when at axon, NT travels in synapse to receptor site

Communicate using local regulators that target cells in the vicinity of emitting cell. Local signaling Target cell Electrical signal along nerve cell triggers release of neurotransmitter Neurotransmitter diffuses across synapse Secretory vesicle Local regulator diffuses through extracellular fluid Figure 11. 4 A B (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. Target cell is stimulated (b) Synaptic signaling. A nerve cell releases neurotransmitter molecules into a synapse, stimulating the target cell.

Long Distance Signaling Endocrine signaling specialized cells release hormone molecules into vessels of the circulatory system to target cells in other parts of the body Long-distance signaling Endocrine cell Blood vessel Hormone travels in bloodstream to target cells Target cell Figure 11. 4 (c) Hormonal signaling. Specialized endocrine cells secrete hormones into body fluids, often the blood. Hormones may reach virtually all C body cells.

The Three Stages of Cell Signaling Earl W. Sutherland Discovered how the hormone epinephrine acts on cells by stimulating the breakdown of glycogen within liver and skeletal muscle cells Sutherland suggested that cells receiving signals went through three processes Reception Transduction Response

3 Stages of Cell Signaling 1. Reception target cell’s detection of the signal 2. Transduction receptor protein changes converting signal to a form that can bring about specific cellular response via a signal transduction pathway 3. Response activation of cellular response

Overview of cell signaling EXTRACELLULAR FLUID 1 Reception CYTOPLASM Plasma membrane 2 Transduction 3 Response Receptor Activation of cellular response Relay molecules in a signal transduction pathway Signal molecule Figure 11. 5

11. 2 Reception Signaling begins with the recognition of a chemical messenger by a receptor protein 1) Intracellular receptors 2) Receptors in the PM The signal molecule (ligand) and receptor are highly specific ex. peptides (short AA chains linked by peptide bonds) A conformational change in a receptor Is often the initial transduction of the signal

1) Intracellular Receptors Intracellular receptors Are cytoplasmic or nuclear proteins To reach the receptor, a chemical messenger passes through the target cell’s PM Ex) steroid hormone testosterone Signal molecules that are small or hydrophobic And can readily cross the plasma membrane use these receptors

INTRACELLULAR RECEPTORS In cytoplasm or nucleus of target cell hydrophobic signaling molecules Steroid hormones Bind to intracellular receptors Hormone EXTRACELLULAR (testosterone) FLUID 1 The steroid hormone testosterone passes through the plasma membrane. Plasma membrane Receptor protein Hormonereceptor complex 2 Testosterone binds to a receptor protein in the cytoplasm, activating it. The hormone 3 DNA Figure 11. 6 receptor complex enters the nucleus and binds to specific genes. m. RNA The bound protein 4 NUCLEUS stimulates the transcription of the gene into m. RNA. CYTOPLASM New protein The m. RNA is 5 translated into a specific protein.

Turning on Genes special proteins called transcription factors control which genes are turned on example: Testosterone (steroid hormone) its activated receptor acts as transcription factor that turns on specific genes thus activated receptor carries out transduction of the signal

2) Receptors in the Plasma Membrane Mostly water-soluble Transmits information from the extracellular environment to the inside of the cell by changing shape when a specific ligand binds to it There are three main types of membrane receptors G-protein-linked receptors Receptor Tyrosine kinases Ligand-gated ion channels

G-protein-linked receptors Signal-binding site Yeast mating factors, epinephrine & other hormones, embryonic development, sensory reception, human diseases and neurotransmitters Inctivate Segment that interacts with G proteins G-protein-linked Receptor Plasma Membrane Activated Receptor Signal molecule GDP CYTOPLASM G-protein (inactive) Enzyme GDP GTP Activated enzyme GTP GDP P i Figure 11. 7 Cellular response enzyme

Receptor Tyrosine Kinases Can trigger Signal-binding sitea Signal multiple molecule Signal pathways Helix in the molecule Membrane essential and growth and Tyrosines reproduction Receptor tyrosine Characterized by kinase proteins CYTOPLASM (inactive monomers) having enzymatic activity (kinase) Membrane receptors that 6 ATP 6 ADP attach Activated tyrosine. Fully activated receptor phosphates to kinase regions tyrosine-kinase (unphosphorylated (phosphorylated tyrosines Tyr Tyr Tyr Figure 11. 7 dimer) Tyr Tyr Tyr P Tyr dimer) Tyr P Tyr Tyr Tyr Dimer Activated relay proteins P Tyr P Tyr P Inactive relay proteins Cellular response 1 Cellular response 2

Ion channel receptors Signal molecule (ligand) • hydrophobic or very small ligands • Signal molecule binds as a ligand to the receptor protein on the extracellular side, the gate opens or closes • examples steroid hormones & thyroid hormones of animals Nervous system Figure 11. 7 Gate closed Ions Ligand-gated ion channel receptor Plasma Membrane Gate open Cellular response Gate close

11. 3 Transduction Signal transduction is the process by which a signal is converted to a cellular response by a cascades of molecular interactions that relay signals from receptors to target molecules in the cell Multistep pathways Can amplify a signal 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

Protein Phosphorylation and Dephosphorylation Many signal pathways Include phosphorylation cascades relay signals from receptors to cell targets, amplifies the signal, results in a response by the cell Phosphorylation cascades A series of protein kinases add a phosphate to the next one in line, activating the protein Then phosphatase enzymes then remove the phosphates, deactivating the protein Activity depends on the balance in the cell between active kinase and phosphatase molecules VIDEO

A phosphorylation cascade Signal molecule Receptor Activated relay molecule Inactive protein kinase 1 ory ph Active protein kinase 3 PP Inactive protein P Finally, active protein 4 kinase 3 phosphorylates a protein (pink) that brings about the cell’s response to the signal. ATP ADP P i PP de Pi ADP a sc Enzymes called protein 5 phosphatases (PP) catalyze the removal of the phosphate groups from the proteins, making them inactive and available for reuse. ATP ca Inactive protein kinase 3 on PP Active protein kinase 2 3 then catalyzes the phosphorylation (and activation) of protein kinase 3. P Active protein kinase 2 ADP i lat ATP Pi os Ph Active protein kinase 1 2 transfers a phosphate from ATP to an inactive molecule of protein kinase 2, thus activating this second kinase. Active protein kinase 1 Inactive protein kinase 2 Figure 11. 8 1 A relay molecule activates protein kinase 1. P Active protein Cellular response

Small Molecules and Ions as Second Messengers First messengers are the extracellular signal molecule that binds to the membrane receptor Not all components of signal transduction pathways are proteins Second messengers are essential to the function of the cascade, transmits the signal from the PM to the metabolic machinery in the cytoplasm Are small, nonprotein, water-soluble molecules or ions readily spread throughout the cell via diffusion Examples: cyclic AMP cyclic GMP calcium ions and IP 3

Cyclic AMP (c. AMP) Epinephrine somehow causes glycogen breakdown without passing through the PM (Southerland) Epinephrine (adrenaline) binds to a receptor on the PM on a liver cell elevating the concentration of c. AMP inside the cell, activating adenylyl cyclase in PM converts ATP into lots of c. AMP carries the signal into the interior of the cell where it initiates glycogen breakdown c. AMP does not last if epinephrine is not present because of phosphodiesterase (turns c. AMP into AMP) more epinephrine is needed to boost amount of c. AMP in cytosol c. AMP activates protein kinase A which causes a cellular response NH 2 N N O O O N N – O P O P O Ch 2 O O O N N O Pyrophosphate P Pi N N Adenylyl cyclase O OH OH ATP NH 2 O CH 2 Phoshodiesterase O P O O OH Cyclic AMP N N O HO P O CH 2 O O H 2 O OH OH AMP

Many G-proteins Trigger the formation of c. AMP, which then acts as a second messenger in cellular pathways video Figure 11. 10

11. 4 Response Concept 11. 4: Cell signaling leads to regulation of cytoplasmic activities or transcription

Cytoplasmic and Nuclear Responses Reception In the cytoplasm Signaling pathways regulate a variety of cellular activities regulating the activity of the enzyme Epinephrine Binding of epinephrine to G-protein-linked receptor (1 molecule) Transduction Inactive G protein Active G protein (102 molecules) Inactive adenylyl cyclase Active adenylyl cyclase (102) ATP Cyclic AMP (104) Inactive protein kinase A In the nucleus Synthesis of m. RNA (transcription) Active protein kinase A (104) Inactive phosphorylase kinase Active phosphorylase kinase (105) Inactive glycogen phosphorylase Active glycogen phosphorylase (106) Response Glycogen Glucose-1 -phosphate (108 molecules)

Epinephrine Same receptor Different response • inhibition or promotion of glycogen

hypothalamus Liver Kidneys Adrenal gland releases adrenaline (epinephrine) Lungs Intestines Circulatory system Heart

Other pathways Regulate genes by activating transcription factors that turn genes on or off regulate the synthesis of enzymes or proteins, unlike EXTRACELLULAR epinephrine Hormone (testosterone) FLUID Growth factor Reception Plasma membrane Receptor protein Phosphorylation cascade Transduction Hormonereceptor complex CYTOPLASM DNA m. RNA NUCLEUS Figure 11. 6 CYTOPLASM New protein Figure 11. 14 Inactive transcription Active transcription factor P DNA Response Gene NUCLEUS m. RNA

Fine-Tuning of the Response Signal pathways with multiple steps Can amplify the signal and contribute to the specificity of the response Signals can be fine tuned in several way Signal Amplification Specificity Efficiency Termination

1) Signal Amplification Each protein in a signaling pathway Amplifies the signal by activating multiple copies of the next component in the pathway Epinephrine triggered pathways: each adenylyl cyclase catalytic event forms more c. AMP molecules and each protein kinase phosphorylation makes more of the next kinase; thus amplifying all the products in transduction making hundreds of millions of glucose molecules from glycogen

2) The Specificity of Cell Signaling Signal molecule The different combinations of proteins in a cell Give the cell great specificity in both the signals it detects and the responses it carries out Pathway branching and “cross-talk” Receptor Relay molecules Cell A. Pathway leads to a single response Response 1 Response 2 3 Cell B. Pathway branches, leading to two responses Further help the cell coordinate incoming signals Activation or inhibition Cell C. Cross Response 4 Response 5 -talk occurs between two pathways Figure 11. 15 Cell D. Different receptor leads to a different response

3) Signaling Efficiency Scaffolding proteins (large relay proteins to which several other relay proteins are simultaneously attached) Can increase the signal transduction efficiency by participating in several pathways Figure 11. 16 Signal molecule Plasma membrane Receptor Scaffolding protein Three different protein kinases

4) Termination of the Signal response is terminated quickly By the reversal of ligand binding Active and inactive forms on the receptor c. AMP to AMP

Real Applications Fight or Flight