AP Biology Notes Outline Enduring Understanding 3.D

L. Carnes

Big Idea 3: Living systems store, retrieve, transmit and respond to information essential to life processes.

Enduring Understanding 3.D:

Cells communicate by generating, transmitting and receiving chemical signals.

Learning Objectives: Essential Knowledge 3.D.1: Cell communication processes share common features that reflect a shared evolutionary history.

– (3.31) The student is able to describe basic chemical processes for cell communication shared across evolutionary lines of descent. – (3.32) The student is able to generate scientific questions involving cell communication as it relates to the process of evolution. – (3.33) The student is able to use representations and models to describe features of a cell signaling pathway.

Essential Knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.

– (3.34) The student is able to construct explanations of cell communication through cell-to-cell direct contact or through chemical signaling. – (3.35) The student is able to create representations that depict how cell-to-cell communication occurs by direct contact or from a distance through

chemical signaling.

Essential Knowledge 3.D.3: Signal transduction pathways link signal reception with cellular response. – (3.36) The student is able to describe a model that expresses the key elements of signal transduction pathways by which a signal is converted to a cellular

response. Essential Knowledge 3.D.4: Changes in signal transduction pathways can alter cellular responses.

– (3.37) The student is able to justify claims based on scientific evidence that changes in signal transduction pathways can alter cellular response. – (3.38) The student is able to describe a model that expresses key elements to show how change in signal transduction can alter cellular response. – (3.39) The student is able to construct an explanation of how certain drugs affect signal reception and, consequently, signal transduction pathways.

Bozeman Instruction Videos: http://www.bozemanscience.com/ap-biology/ 3.D.1 - #036: Evolution of Cell Communication 3.D.2 - #037: Cell Communication 3.D.3 - #038: Signal Transduction in Pathways 3.D.4 - #039: Effects of Changes in Pathways

Required Readings: 3.D.1 – Ch. 11 & Ch. 45 3.D.1 – Article: Molecular Mechanisms of Mammalian DNA Repair 3.D.2 – Ch. 11 & Ch. 45 3.D.3 – Ch. 11 & Ch. 45 3.D.4 – Ch. 11 & Ch. 45

Practicing Biology Homework Questions: Questions #40-51

Essential Knowledge 3.D.1: Cell communication processes share common features that reflect a shared evolutionary history.

For cells to function in a biological system, they must communicate with other cells and respond to their external environment. Cell-to-cell communication is ubiquitous in biological systems, from archaea and bacteria to multicellular organisms. The basic chemical processes by which cells communicate are shared across evolutionary lines of descent, and communication schemes are the products of evolution. Cell-to-cell communication is a component of higher-order biological organization and responses. In multicellular organisms, cell-to-cell and environment-to-cell chemical signaling pathways direct complex processes, ranging from cell and organ differentiation to who organism physiological responses and behaviors.

Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment. Organisms share many conserved core processes and features that are widely distributed among organisms today. These processes provide evidence that all organisms (Archaea, Bacteria, and Eukarya, both extant and extinct) are linked by lines of descent from common ancestry.

• The existence of these properties in organisms today implies that they were present in a universal ancestor and that present life evolved from a universal ancestor.

• Cell-to-cell communication is a component of higher-order biological organization and responses. Correct and appropriate signal transduction processes are generally under strong selective pressure. For cells to function in a biological system, they must communicate with other cells and respond to their external environment.

• Cell-to-cell communication is ubiquitous in biological systems, from Archaea and Bacteria to multicellular organisms. • The basic chemical processes by which cells communicate are shared across evolutionary lines of descent, and

communication schemes are the products of evolution. In single-celled organisms, signal transduction pathways influence how the cell responds to its environment. Unicellular organisms gather information about their environment and respond to it by using signaling pathways triggered by chemicals in the environment. These chemicals can relay information about how close a food source is, how many of the same bacteria are nearby, or the location of a favorable environment. Chemical substances produced by unicellular organisms can also be used to communicate between individual cells and influence their cellular processes.

• Illustrative Examples include: – The use of chemical messengers by microbes to communicate with other nearby cells and to regulate specific

pathways in response to population density (quorum sensing). – Response to external signals by bacteria that influences cell movement (chemotaxis).

Quorum Sensing in Unicellular Organisms http://www.youtube.com/watch?v=YJWKWYQfSi0

Quorum sensing is a cell density-dependent signal transduction system, which controls a variety of the physiological behavior in bacteria.

During quorum sensing, bacteria produce and secrete the small signal molecules outside the cell to recognize the population density.

These signal molecules are accumulated outside the cell during the cell growth.

When the concentration of the signal molecules reaches threshold level, the signal transduction cascade activates the expression of certain genes.

Accordingly, strain specific behavior, like a genetic competence of streptococci, bacteriocin production of lactic acid bacteria, sporulation of Bacillus subtilis and virulence expression of Staphylococcus aureus, is induced in concert by all bacteria in the population.

Chemotaxis in Unicellular Organisms http://highered.mcgraw-hill.com/sites/007337525x/student_view0/exercises_35-90/chemotaxis_in_e__coli.html Chemotaxis is the movement or orientation of an organism along a chemical concentration gradient either toward or away from a chemical stimulus. Chemotaxis in bacteria is controlled by signal transduction, which affects the direction of flagella rotation (clockwise rotation causes tumbling). This is the native condition of the bacteria (occurs without receptor stimulation).

Tumbling at random occurs when the molecule CheA activates the molecule CheY, which attaches to the flagellum motor and causes its clockwise rotation.

When an attractant molecule is encountered, the action of CheA is inhibited so that it can’t activate CheY. At this point, flagellum rotation is counter-clockwise, causing the bacterium to swim straight (a run).

Encountering more attractant molecules will cause even more runs and less tumbling – the bacteria move in the direction of the stimulus.

In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a whole. As with unicellular organisms, multicellular organisms usually communicate via chemical messengers targeted for cells that may or may not be immediately adjacent. Cells may communicate via direct contact, or communication may involve chemical signaling over short and long distances.

• Illustrative Examples include: – Epinephrine stimulation of glycogen breakdown in mammals. – Temperature determination of sex in some vertebrate organisms. – DNA repair mechanisms.

Epinephrine Stimulation of Glycogen Breakdown in Animals http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter17/animation__second_messenger__camp.html The binding of epinephrine to the plasma membrane of a liver cell elevates the cytosolic concentration of a compound called cyclic adenosine monophosphate (cyclic AMP or cAMP). An enzyme embedded in the plasma membrane converts ATP to cAMP in response to an extracellular signal (epinephrine). Note that epinephrine doesn’t stimulate the process directly – but rather binds to a specific receptor protein initiating the protein to activate a secondary messenger (cAMP) in the pathway. The activation of the secondary messenger triggers a liver or muscle cell to break down glycogen. Temperature Determination of Sex in Some Vertebrate Organisms In some vertebrates, the sex of the offspring of this system is determined by the temperature of the eggs. Instead of chromosomal sex determination systems, this is an environmental sex determination system. The eggs are affected by the temperature at which they are incubated during the middle one-third of embryonic development. This critical period of incubation is known as the thermo-sensitive period (TSP). Illustrative example:

Estrogen is critical for ovarian development in all vertebrate groups except for placental mammals. Exogenous (not synthesized within the organism or system) estrogen treatment during development will transiently sex-reverse chickens, and permanently sex-reverse reptiles, amphibians, and fish.

In the slider turtle, administration of exogenous estradiol (E2) to an egg incubating at a male-producing temperature, as well as administration of an aromatase inhibitor (AI), which prevents estrogen production, to an egg incubating at a female-producing temperature, will override the temperature cue and redirect the sexual fate of the embryo.

Importantly, warm temperature and estrogen act synergistically (interaction of discrete agents whereby the total effect is greater than individual effects) – less estrogen is required to sex-reverse embryos from intermediate temperatures than from extreme male-producing temperatures.

Because estrogen can override a temperature cue, estrogen production has been proposed to be the proximate mechanism through which temperature exerts its actions.

Essential Knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.

Certain signal pathways involve direct cell-to-cell contact, operate over very short distances, and may be determined by the structure of the organism or organelle, including plasmodesmata in plants and receptor-to-recognition protein interaction in the vertebrate immune system. Chemical signals, however, allow cells to communicate without physical contact. The distance between signal generating cell(s) and the responding cell can be small or large. In this type of signaling pathway, there is often a gradient response, and threshold concentrations are required to trigger the communication pathway. Direct Contact vs. Chemical Signaling Remember, cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.

• Direct cell-to-cell contact: – Immune cell interaction via antigen-presenting cells. – Plasmodesmata between plant cells that allow material to be transported from cell to cell.

• Communication over short distance: – Quorum sensing in bacteria. – Neurotransmitters.

• Long distance signaling: – Hormones are produced in one area of the body, released into the blood stream, and can travel long distances to

initiate response in another area of the body (insulin, HGH, testosterone, estrogen). Cells communicate by cell-to-cell contact. Cell Junctions: both animals and plants have cell junctions that allow molecules to pass readily between adjacent cells without crossing plasma membranes. Cell-cell Recognition: Two cells in an animal may communicate by interaction between molecules protruding from their surface. In multi-celled organisms, individual cells must communicate and join with one another to create a harmonious organism. Cell junctions can be classified in four functional groups:

1. Tight junctions 2. Desmosomes 3. Gap junctions 4. Plasmodesmata

Neighboring cells often adhere, interact, and communicate through special patches of direct physical contact…intracellular junctions help integrate cells! At tight junctions, membranes of neighboring cells are pressed together, preventing leakage of extracellular fluid Desmosomes (anchoring junctions) fasten cells together into strong sheets Gap junctions (communicating junctions) provide cytoplasmic channels between adjacent cells

Plasmodesmata are channels that perforate plant cell walls. Through plasmodesmata, water and small solutes (and sometimes proteins and RNA) can pass from cell to cell. Plasmodesmata connect one plant cell to the next – they are analogous to gap junctions in animal cells. Cell-to-cell recognition is the cell’s ability to distinguish one type of neighboring cell from another and is crucial to the functioning of a multicelled organism.

• A feature of cells that aids in cell communication is the glycocalyx, which consists of oligosaccharides (small chains of sugar molecules) attached to integral proteins within the plasma membrane.

• The glycocalyx is responsible for contact inhibition, the normal trait of cells to stop dividing when they become too crowded.

Illustrative Examples – Cells communicate by cell-to-cell contact – WATCH THE VIDEOS! • Immune Cell Interaction

– http://highered.mcgraw-hill.com/sites/0072507470/student_view0/chapter22/animation__the_immune_response.html

• Plasmodesmata – http://highered.mcgraw-

hill.com/olcweb/cgi/pluginpop.cgi?it=swf::600::480::/sites/dl/free/007353224x/788092/Water_Uptake.swf::Water+Uptake

Cells communicate over short distances by using local regulators that target cells in the vicinity of the emitting cell. Cells in multicellular organisms usually communicate via chemical messengers targeted for cells that may or may not be immediately adjacent. In many cases, messenger molecules are secreted by the signaling cell and travel SHORT DISTANCES. These messenger molecules are known as local regulators, and they have strong influence on cells in the vicinity, known as target cells. Illustrative examples include (WATCH THE VIDEOS)!: 1. Neurotransmitters

– https://highered.mcgraw-hill.com/sites/0072495855/student_view0/chapter14/animation__transmission_across_a_synapse.html

2. Plant Immune Responses – http://bcs.whfreeman.com/thelifewire/content/chp40/4001s.swf

3. Quorum Sensing in Bacteria – http://highered.mcgraw-

hill.com/olcweb/cgi/pluginpop.cgi?it=swf::500::500::/sites/dl/free/0073375225/594358/QuorumSensing.swf::Quorum+Sensing

4. Morphogens in Embryonic Development – http://nortonbooks.com/college/biology/animations/ch29a08.htm

Example #1: http://sites.sinauer.com/neuroscience5e/animations07.01.html • Local regulators in animals called growth factors consist of compounds that stimulate nearby target cells to grow and divide.

Numerous cells can simultaneously receive and respond to the molecules of growth factor produced by a single cell in their vicinity. This type of signaling in animals is referred to as paracrine signaling.

Example #2: http://sites.sinauer.com/neuroscience5e/animations07.01.html • Synaptic signaling occurs in the animal nervous system. An electrical signal along a nerve cell triggers the secretion of a

chemical signal carried by neurotransmitter molecules. These diffuse across the synapse (narrow space between the nerve cell and its target cell). The neurotransmitter stimulates the target cell.

Signals released by one cell type can travel long distances to target cells of another cell type. Both animals and plants use chemicals called hormones for long-distance signaling. Endocrine signals are produced by endocrine cells that release signaling molecules, which are specific and can travel long distances through the blood to reach all parts of the body. Illustrative Examples Include (WATCH THE ANIMATIONS):

1. Insulin: http://vcell.ndsu.edu/animations/insulinsignaling/movie-flash.htm 2. Thyroid Hormone: http://highered.mcgraw-

hill.com/sites/9834092339/student_view0/chapter46/mechanism_of_thyroxine_action.html 3. Human Growth Hormone – RESEARCH ON YOUR OWN. 4. Testosterone & Estrogen – RESEARCH ON YOUR OWN.

Review: The Cellular Internet – WATCH THE ANIMATION! http://www.biopsychology.com/6e/activity0502.html

Essential Knowledge 3.D.3: Signal transduction pathways link signal reception with cellular response.

Chemical signaling pathways in cells are determined by the properties of the molecules involved, the concentration s of signal and receptor molecules, and the binding affinities (fit) between signal and receptor. The signal can be a molecule or a physical or environmental factor. At the cellular level, the receptor is a protein with specificity for the signal molecule; this allows the response pathway to be specific and appropriate. The receptor protein often is the initiation point for a signal cascade that ultimately results in a change in gene expression, protein activity, or physiological state of the cell or organism, including cell death (apoptosis). Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein. Different receptors recognize different chemical messengers, which can be peptides, small chemicals or proteins, in a specific one-to-one relationship. A receptor protein recognizes signal molecules, causing the receptor protein’s shape to change, which initiates transduction of the signal. Illustrative Examples Include:

• G-protein linked receptors: http://bcs.whfreeman.com/thelifewire/content/chp15/15020.html • Ligand-gated ion channels: https://highered.mcgraw-

hill.com/sites/0072495855/student_view0/chapter2/animation__receptors_linked_to_a_channel_protein.html • Receptor tyrosine kinases: http://www.wiley.com/college/fob/quiz/quiz21/21-15.html

Signal transduction is the process by which a signal is converted to a cellular response. The signal transduction pathway relies on plasma membrane proteins in a multi-step process in which a small number of extracellular signal molecules produce a major (amplified) cellular response. Essentially, these pathways convert signals on a cell’s surface into cellular responses. Three stages occur in this type of cell signaling: (1) RECEPTION; (2) TRANSDUCTION; and (3) RESPONSE:

• In reception, the signal molecule, commonly a protein that does not enter the cell, binds to a specific receptor on the cell surface, causing the receptor molecule to undergo a change in conformation.

• This conformational change leads to transduction – a change in signal form, where the receptor relays a message to a secondary messenger.

• This secondary messenger, such as cyclic AMP (cAMP), induces a response within the cell.

Signaling cascades relay signals from receptors to cell targets, often amplifying the incoming signals, with the result of appropriate responses by the cell. Second messengers are often essential to the function of the cascade (i.e. cyclic AMP, calcium ions, etc.) Many signal transduction pathways include:

Protein modifications (i.e. how methylation changes the signaling process).

Phosphorylation cascades in which a series of protein kinases add a phosphate group to the next protein in the cascade sequence.

There are three main types of membrane receptors (1) G-protein-linked; (2) Tyrosine kinases; and (3) Ligand-Gated Ion channel

G-Linked Protein Receptor

Tyrosine-Kinase Receptor

In the absence of the extracellular signal molecule specific for the receptor, all three proteins are in inactive form. When the signal molecule binds to the receptor, the receptor changes shape in such a way that it binds and activates the G protein.

• A molecule of GTP replaces the GDP on the G protein. • The active G protein moving freely along the membrane binds to and activates the enzyme which triggers

the next step in the pathway leading to the cell’s responses. • The G protein then catalyzes the hydrolysis of it GTP and dissociates from the enzyme, becoming available

for future use.

When signal molecules (such as a growth factor) attach to their

binding sites, two polypeptides aggregate, forming a dimer.

Using phosphate groups from ATP, the tyrosine-kinase region of

each polypeptide phosphorylates the tyrosines on the other

polypeptide.

Now fully activated, the receptor protein can bind specific

intracellular proteins – this activates the relay proteins.

Each of these proteins can then initiate a signal transduction

pathway leading to a specific cellular response. Tyrosine-kinase

receptors often activate several different signal-transduction

pathways at once.

Ligand-Gated Ion Channel

Essential Knowledge 3.D.4: Changes in signal transduction pathways can alter cellular response.

Defects in any part of the signal pathway often lead to severe or detrimental conditions such as faulty development, metabolic diseases, cancer or death. Understanding signaling pathways allows humans to modify and manipulate biological systems and physiology. An understanding of the human endocrine system, for example, allowed the development of birth control methods, as well as medicines that control depression, blood pressure and metabolism. Other examples include the ability to control/modify ripening in fruit, agricultural production (growth hormones) and biofilm control. Conditions where signal transduction is blocked or defective can be deleterious, preventative or prophylactic. Illustrative Examples Include:

• Diabetes, heart disease, neurological disease, autoimmune disease, cancer, cholera. • Effects of neurotoxins, poisons, pesticides. • Drugs (anesthetics, antihistamines, birth control). • http://www.wiley.com/college/boyer/0470003790/animations/signal_transduction/signal_transduction.htm

Example: Antihistamines block the release of histamine in the mast cell.

• When an antigen binds to IgE on the mast cell there is a signal transduction pathway that causes the release of histamine and other vasoactive amines from the mast cell granules.

• Antihistamines block this signal transduction. • Altered cell response = decreased/blocked degranulation.

Specific signal molecules cause ligand-gated ion channels in a membrane to open or close, regulating the flow

of specific ions.

This receptor is a transmembrane protein in the plasma membrane that opens to allow the flow of a specific

kind of ion across the membrane when a specific signal molecule binds to the extracellular side of the protein.