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Cell Communication per Parrott
Cell communication processes share common features that reflect a shared evolutionary
history.a. Communication involves transduction of stimulatory or inhibitory signals
from other cells, organisms or the environment. b. Correct and appropriate signal transduction processes are generally under
strong selective pressure.c. In single-celled organisms, signal transduction pathways influence how the
cell responds to its environment.– • Use of chemical messengers by microbes to communicate with other nearby cells
and to regulate specific pathways in response to population density (quorum sensing)– • Use of pheromones to trigger reproduction and developmental pathways– • Response to external signals by bacteria that influences cell movement
d. In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a whole.
– • Epinephrine stimulation of glycogen breakdown in mammals– • Temperature determination of sex in some vertebrate organisms– • DNA repair mechanisms
Local (Short-Distance) Signaling
• Cells may communicate by direct contact– Plasmodesmata in plant cells– Gap junctions in animal cells
• allow ions & currents to flow directly from cell to cell -- used in smooth muscle → synchronized contractions.
• Animal cells can also use cell-cell recognition– Membrane-bound surface molecules can interact and communicate
Local (Short-Distance) Signaling• Messenger molecules can also be secreted by the signaling cell
• Paracrine Signaling:– One cell secretes (releases) molecules that act on nearby “target” cells– Example: growth factors
• Juxtacrine Signaling. – Cell surface proteins from two different cells contact -- used in immune system. Similar to
basic system, but signal molecule is not secreted -- remains on cell surface.• Synaptic Signaling:
– Nerve cells release chemical messengers (neurotransmitters) that stimulate the target cell
Major types of secreted Signals -- classified by type of cell that makes them and/or target location.
1. Endocrine: • Signal molecule secreted by specialized cells in ductless (endocrine) gland• Gland secretes signal molecule (hormone) into blood. • Target cell is often far away. Acts long range. • Examples: Insulin, estrogen, TSH (thyroid stimulating hormone) & TH
(thyroid hormone)
2. Paracrine: • Usually secreted by ordinary cells • Target cell is near by -- Receptor is on adjacent cells. Act locally.
o histamines (mediate allergic reactions, responses to inflammation) o prostaglandins -- initiate uterine cramps; cause fever in response to bacterial infection. o Many growth factors (like EGF)
3. Autocrine: • Like paracrine, except receptor is on same cell. ex. = some growth factors
4. Neurocrine: • Neuron secretes signal molecule.• Signal molecule acts as a neurotransmitter (NT)• NT acts on receptors on neighbor (gland, another neuron or muscle). Acts
locally, like a paracrine. • Examples: norephinephrine, acetyl choline.
5. Neuroendocrine: • Neuron secretes signal molecule, as in previous case.• Signal molecule acts like a hormone (travels through blood to target). • Example: Epinephrine (adrenaline).
6. Exocrine: • Exocrine gland secretions are released by ducts to outside of body (or to
inside of body cavity)*. • Secretions on outside can carry signals → target in different individual =
pheromones (detected by olfactory receptors in mammals).
Chemical Communication
Long-Distance Signaling
• Endocrine (hormone) signaling– Specialized cells release
hormone molecules, which travel (usually by diffusion through cells or through the circulatory system) to target cells elsewhere in the organism
Three Stages of Cell SignalingThere are 3 stages at the “receiving end” of a cellular conversation:
– In reception, a chemical signal binds to a cellular protein, typically at the cell’s surface (may also bind intracellularly).
– In transduction, binding leads to a change in the receptor that triggers a series of changes along a signal-transduction pathway.
– In response, the transduced signal triggers a specific cellular activity.
Stage 1: Reception• The target cell “detects” that there is a signal molecule
coming from outside the cell– The signal is detected when it binds to a protein on the cell’s
surface or inside the cell– The signal molecule “searches out” specific receptor
proteins • The signal molecule is a ligand
– It is a molecule that specifically binds to another one (think enzymes!)
Stage 2: Transduction• This stage converts the signal into a form that
can bring about a specific cellular response– One signal-activated receptor activates another
protein, which activates another molecule, etc., etc. (relays)
– These act as relay molecules– Often the message is transferred using protein
kinases, which transfer phosphate groups from ATP molecules to proteins
Stage 3: Response• The signal that was
passed through the signal transduction pathway triggers a specific cellular response– Examples: enzyme action,
cytoskeleton rearrangement, activation of genes, etc., etc.
– Diagram example: transcription of mRNA
The Specificity of Cell Signaling• The particular proteins
that a cell possesses determine which signal molecules it will respond to and how it will respond to them
• Liver cells and heart cells, for example, do not respond in the same way to epinephrine because they have different collections of proteins
Signal Transduction
• Reception
• Transduction
• Response
2 Types of Signals• Lipid-soluble steroids &
thyroid hormones– Diffuse through plasma mem.– Enter nucleus– Form “hormone-receptor
complex”– H-R complex binds as
transcription factors to chromosome to activate/ inactivate gene(s)
– i.e. NO
• Peptides & water-soluble amines– Hormone (A) binds to
receptor on cell surface– Activates G- protein– Activates adenylate cyclase
• Converts ATP to cAMP– cAMP activates protein
kinases, which produce final effect.
Types of Receptors• On Cell Surface -- for water soluble signals. Three major kinds
of cell surface receptors -- – G Protein Linked Receptors; Also called G Protein Coupled Receptors or GPCRs.
(TSH & epinephrine use these.) – Protein Kinase (usually TK) Linked Receptors. These generate
cascades of modifications, but do not always use 2nd messengers. – Ion Channels. Receptor is part of an ion channel. (Neurons)
• Intracellular -- for lipid soluble signals. All similar, all TF's. Receptors are transmembrane proteins with an extracellular binding domain for signal. These are sometimes called "extracellular receptors" but only ligand binding domain is extracellular, not the entire protein.
Signal Transduction Pathway Animation
Transduction Pathway Epinephrine
• Ligand for Cell Surface Receptor– (hydrophilic: don’t cross plasma
membrane)
– Ion-Channel-Linked Receptors• convert chemical to electrical
signals
– G-protein-linked Receptors• ligand binding G-Protein
activation by exchange bound GDP for GTP
• Common structure = 7-pass membrane protein
– Enzyme-Linked Receptors
Cell Signaling: Extracellular
Extracellular Signaling Molecules
• Many are Molecular Switches– switched on by signaling molecule, must also be turned
off
• Most common switching mechanisms (nicotine, morphine &
heroin)
– phosphorylation• signal activated kinase; (kinase = enzyme that
phosphorylates a protein)• dephosphorylation – phosphatase
– GTP binding proteins:– GDP bound = inactive, – GTP bound = active
G-Protein Linked Receptors
•Some activate membrane-bound enzymes => increase “2nd messengers”
– Small and water soluble and easily diffuse– 2nd messenger = cAMP
• adenyl cyclase => ATP to cAMPcAMP phosphodiesterase => cAMP to ATPcAMP dependent protein kinase activation by CampcAMP => both rapid and slow responses
– 2nd messengers = IP3 & DAGphospholipase c => IP3 & DAGIP3 => opens ER Ca+2 channels . >>>> cytoplasmic Ca+2.
> free Ca+2 => many effectsDAG (w free Ca+2) => activated PKC to inner face of
membraneactivated PKC => many effects
– 2nd messenger = Ca+2free Ca+2 => many effect via Ca+2 binding proteins
e.g. calmodulin & calmodulin dependent protein kinases
• The G protein acts as an on-off switch.– If GDP is bound, the G protein is
inactive.– If GTP is bound, the G protein is active.
Some regulate ion channels Some activate membrane-bound enzymes increase “2nd messengers”
2nd messenger = cAMP 2nd messengers = IP3 & DAG
Copyright © 2005 Pearson Prentice Hall, Inc.
16_23_slowly_rapidly.jpg
Cell Signaling: Intracellular
Signaling Pathways: – Same receptor molecule can
interact w/many intracellular relay systems so same signal & same receptor different effects in different cells
– Same relay system many act on many different intracellular targets
Signaling CascadeCritical Functions•Transduce Signal•Relay signal from point of reception to point of response production•Amplify signaling molecules are found in such [low] that the effect would be minimal w/o amplification•Distribute signal to >1 process simultaneously•Modulate signal to fit other internal & external conditions
Cells communicate with each other through direct contact with other cells or from a
distance via chemical signaling.a. Cells communicate by cell-to-cell contact.
– • Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells and killer T-cells.
– • Plasmodesmata between plant cells that allow material to be transported from cell to cell.
b. Cells communicate over short distances by using local regulators that target cells in the vicinity of the emitting cell.
– • Neurotransmitters– • Plant immune response– • Quorum sensing in bacteria– • Morphogens in embryonic development
c. Signals released by one cell type can travel long distances to target cells of another cell type.
– 1. 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.
• Insulin• Human growth hormone• Thyroid hormones• Testosterone• Estrogen
Cell Signaling• SIGNALING PATHWAYS CAN BE HIGHLY INTERCONNECTED
F16-38
• (like nerve networks in brain or microprocessors in a computer)
• “... a major challenge to figure out how cell communication pieces fit togetherto allow cells to integrate environmental signals and to respond appropriately”
Death Signaling, 2, 3
Cell Signaling in PlantsSignaling Between Plants & Pathogens
Phytochrome signaling
Resources• Pathophysiology of the Endocrine System• Signal Transduction Pathways• Cell-Cell Adhesion in Leukocyte Extravasation• Fight or Flight Response • Fibroblast Cell Signals• Fight or Flight 2• Cell Signaling Links• Bozeman Signal Transduction Pathways• Signal Transduction by Extracellular Receptors Tutorial• Cell Signaling Flash Movies• p53 Song• Apoptosis Animation
Essential knowledge 3.D.1: Cell communication processes share common features that reflect a shared evolutionary history.• a. Communication involves transduction of stimulatory or inhibitory signals from other cells, organisms or the environment. [See also 1.B.1]• b. Correct and appropriate signal transduction processes are generally under strong selective pressure.• c. In single-celled organisms, signal transduction pathways influence how the cell responds to its environment.• • chemical messengers by microbes to communicate with nearby cells and regulate specific pathways in response to population density (quorum sensing),
pheromones to trigger reproduction & developmental pathways, Response to external signals by bacteria that influences cell movement• d. In multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a whole.• LO 3.31 The student is able to describe basic chemical processes for cell communication shared across evolutionary lines of descent. [See SP 7.2]• LO 3.32 The student is able to generate scientific questions involving cell communication as it relates to the process of evolution. [See SP 3.1]• LO 3.33 The student is able to use representation(s) and appropriate models to describe features of a cell signaling pathway. [See SP 1.4]
Essential knowledge 3.D.2: Cells communicate with each other through direct contact with other cells or from a distance via chemical signaling.• a. Cells communicate by cell-to-cell contact.• • Immune cells interact by cell-cell contact, antigen-presenting cells (APCs), helper T-cells and killer T-cells. [See also 2.D.4]• • Plasmodesmata between plant cells that allow material to be transported from cell to cell.• b. Cells communicate over short distances by using local regulators that target cells in the vicinity of the emitting cell.• • Neurotransmitters • Plant immune response • Quorum sensing in bacteria • Morphogens in embryonic development
Essential knowledge 3.D.3: Signal transduction pathways link signal reception with cellular response.• a. Signaling begins with the recognition of a chemical messenger, a ligand, by a receptor protein.• 1. Different receptors recognize different chemical messengers, which can be peptides, small chemicals or proteins, in a specific one-to-one relationship.• 2. A receptor protein recognizes signal molecules, causing the receptor protein’s shape to change, which initiates transduction of the signal.• • G-protein linked receptors • Ligand-gated ion channels • Receptor tyrosine kinases• b. Signal transduction is the process by which a signal is converted to a cellular response.• 1. Signaling cascades relay signals from receptors to cell targets, often amplifying the incoming signals, with the result of appropriate responses by the cell.• 2. Second messengers are often essential to the function of the cascade.• • Ligand-gated ion channels • Second messengers, such as cyclic GMP, cyclic AMP calcium ions (Ca2+), and inositol triphosphate (IP3)• 3. Many signal transduction pathways include:• i. Protein modifications (an illustrative example could be how methylation changes the signaling process)• ii. Phosphorylation cascades in which a series of protein kinases add a phosphate group to the next protein in the cascade sequence• LO 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 response.• a. Conditions where signal transduction is blocked or defective can be deleterious, preventative or prophylactic.• • Diabetes, heart disease, neurological disease, autoimmune disease, cancer, cholera• • Effects of neurotoxins, poisons, pesticides• • Drugs (Hypertensives, Anesthetics, Antihistamines and Birth Control Drugs)