Cell Communication

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Cell Communication
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The Cellular Internet

• Within multicellular organisms, cells must
  communicate with one another to coordinate their
  activities
• A signal transduction pathway is a series of
  steps by which a signal on a cells surface is
  converted into a specific cellular response
• Signal transduction pathways are very similar in
  all organisms, even organisms as different as
  unicellular yeasts and multicellular mammals

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Local (Short-Distance) Signaling

• Cells may communicate by direct contact
• Plasmodesmata in plant cells
• Gap junctions in animal cells
• Animal cells can also use cell-cell recognition
• Membrane-bound surface molecules can interact and
  communicate

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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
• Synaptic Signaling
• Nerve cells release chemical messengers
  (neurotransmitters) that stimulate the target cell

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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

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The Three Stages of Cell Signaling

• There are 3 stages at the receiving end of a
  cellular conversation
• Reception
• Transduction
• Response

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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 cells surface or inside the cell
  (receptor protein)
• The signal molecule searches out specific
  receptor proteins
• The signal molecule is a ligand
• It is a molecule that specifically binds to
  another one and induces a change in the shape of
  the receptor protein
• Ligands can be hydrophobic or hydrophillic

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Receptor proteins

• There are 2 different types of receptor proteins
  
• Membrane receptors transmembrane proteins
• Intracellular receptors proteins that occur in
  the cytoplasm or the nucleus

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Second messengers

• Molecules that relay messages from membrane
  receptors to other molecules
• They are all
• Small, nonprotein molecules
• Either hydrophillic, hydrophobic, or gaseous
• Ex. Ca ions, IP3, CAMP, and DAG

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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. - this is called a signaling cascade
• These act as relay molecules
• Often the message is transferred using protein
  kinases, which transfer phosphate groups from ATP
  molecules to proteins
• These can be very complicated

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Stage 2 Transduction
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Advantages of signal transduction

• Amplification the effect of the signaling
  molecule can be amplified
• Control the cell can control the accuracy of the
  signaling
• Multiplicity a signaling molecule can start many
  different processes at once to respond to the
  signal

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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

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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

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Receptors and their responses
Receptor Receptor description Ligand (1st messengers) Supporting mechanisms Cellular response examples
Gated ion receptor Types ligand gated ion receptor Voltage gated ion receptor Ligand Acetylcholine Voltage Change in membrane voltage None Ligand Na gate opens nerve impulse or muscle contraction Voltage Na, K gates open, nerve transmission
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Receptors and their responses
Receptor Receptor description Ligand (1st messengers) Supporting mechanisms Cellular response examples
G Protein Coupled Receptor (GPCR) GPCR Gprotein Effector protein Various Enzymatic effector protein 2ndmessengers cAMP IP3 / DAG Ca2 EEF enzyme activity cAMP glycogen ? glucose IP3 releases Ca2 as a second messenger Ca2 causes muscle contraction
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Receptors and their responses
Receptor Receptor description Ligand (1st messengers) Supporting mechanisms Cellular response examples
Protein Kinase Receptor Types Receptor Tyrosine Kinase (RTK) Receptor Serine/ Threonine Kinase RTK Insulin RS/TK Mitogens, growth factors RTK multiple kinase cascades RS/TK Ras (g protein) Mitogen kinase cascade RTK glucose to glycogen RS/TK Activation of transcription factors that promote growth and cell differentiation
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Receptors and their responses
Receptor Receptor description Ligand (1st messengers) Supporting mechanisms Cellular response examples
Intracellular receptor Cytoplasmic or nuclear receptors Steroid hormones (testosterone estrogen) Development of primary and secondary sex characteristics
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When cell signaling doesnt work

• Signal transduction pathways can be blocked or
  defective
• Examples
• Diabetes
• Cholera
• Autoimmune disease
• Cancer
• Neurotoxins, poisons, pesticides
• Drugs (anesthetics, antihistamines, blood
  pressure meds)

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Cholera

• Toxin modifies G-protein involved in regulating
  salt water secretion
• G protein stuck in active form ? intestinal cells
  secrete salts, water
• Infected person develops profuse diarrhea and
  could die from loss of water and salts

• Disease acquired by drinking contaminated water
  (w/human feces)
• Bacteria (Vibrio cholerae) colonizes lining of
  small intestine and produces toxin

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Apoptosis cell suicide

• Cell is dismantled and digested
• Triggered by signals that activate cascade of
  suicide proteins (caspase)
• Why?
• Protect neighboring cells from damage
• Animal development maintenance
• May be involved in some diseases (Parkinsons,
  Alzheimers)
• Interference may contribute to cancers

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Apoptosis of a human white blood cell

• Left Normal WBC
• Right WBC undergoing apoptosis shrinking and
  forming lobes (blebs)

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Effect of apoptosis during paw development in the
mouse
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Drugs

• There are drugs that interfere with cell
  signaling
• can either be agonists or antagonists
• Agonists acts the same way that a ligand does
• Antagonists blocks the binding site of the
  receptor and does not let cell signaling occur
• Ex. The poison curare blocks the binding sites
  for the chemical acetylcholine which will cause
  muscle paralysis and death