Signal transmission and signal transduction

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Signal transmission and signal transduction

• Xia Qiang, MD PhD
• Department of Physiology
• Rm C518, Block C, Research Building, School of
  Medicine
• Tel [phone]
• Email xiaqiang_at_zju.edu.cn

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OUTLINE

• Intercellular signal transmission
• Chemical transmission
• Electrical transmission
• Signal transduction pathway
• Pathways initiated by intracellular receptors
• Pathways initiated by plasma membrane receptors

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Intercellular signal transmission

• Chemical transmission
• Chemical signals
• Neurotransmitters

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Intercellular signal transmission

• Chemical transmission
• Chemical signals
• Neurotransmitters
• Humoral factors
• Hormones
• Cytokines
• Bioactivators

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Intercellular signal transmission

• Chemical transmission
• Chemical signals
• Neurotransmitters
• Humoral factors
• Gas NO, CO, etc.

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Intercellular signal transmission

• Chemical transmission
• Chemical signals
• Receptors
• Membrane receptors
• Intracellular receptors

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Receptors on the surface of a cell are
typically proteins that span the membrane
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Only Cell A has the matching receptors for this
chemical messenger, so it is the only one that
responds
Cells B C lack the matching receptors Therefore
are not directly affected by the signal
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Intercellular signal transmission

• Electrical transmission
• Gap junction

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Cardiac Muscle
Low Magnification View
The intercalated disk is made of several types of
intercellular junctions. The gap junction
provides a low resistance pathway for the action
potential to spread from cell to cell
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Signal transduction pathway

• Pathways initiated by intracellular receptors
• Pathways initiated by plasma membrane receptors

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This hydrophobic signal requires a carrier
protein while in the plasma
but at the target cell the signal moves easily
through the membrane and binds to its receptor
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Signal transduction pathway

• Pathways initiated by intracellular receptors
• Pathways initiated by plasma membrane receptors
  (transmembrane signal transduction)

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Transmembrane signal transduction
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Transmembrane signal transduction

• Mediated by G protein-linked receptor
• Mediated by enzyme-linked receptor
• Mediated by ion channel

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Binding of ligands to membrane-spanning
receptors activates diverse response mechanisms
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Transmembrane signal transduction

• Mediated by G protein-linked receptor
• Mediated by enzyme-linked receptor
• Mediated by ion channel

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The Nobel Prize in Physiology or Medicine 1994

• "G-proteins and the role of these proteins in
  signal transduction in cells"

Alfred G. Gilman
Martin Rodbell
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The Discovery of G Proteins
Normal Lymphoma Cell
Mutated Lymphoma Cell
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Activation and Inactivation of the G Protein
1. The G protein, composed of alpha-, beta- and gamma-subunits, in its resting state with bound GDP. 2. The receptor with bound hormone activates the G protein and replaces GDP...
3. ...with GTP and the G proteins is activated. The subunits separate. 4. Some seconds later the GTP, bound to the alpha-subunit, is hydrolysed to GDP. The subunits recombine.
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G-protein-coupled Receptors
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• Signaling molecules involved

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Main signaling pathways

• (1) cAMP-PKA pathway
• (2) IP3-Ca2 pathway
• (3) DG-PKC pathway
• (4) G protein-ion channel pathway

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• cAMP-PKA pathway
• Gs, Gi

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The cyclic AMP second messenger system
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Adenylyl cyclase forms cAMP, a second messenger
that activates enzymes used in cellular
responses
The phosphodiesterase enzymes terminate
the second messenger cAMP
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The cAMP system rapidly amplifies the
response capacity of cells here, one first
messenger led to the formation of one million
product molecules
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Cells can respond via the cAMP pathways using a
diversity of cAMP-dependent enzymes,
channels, organelles, contractile filaments, ion
pumps, and changes in gene expression
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• (2) IP3-Ca2 pathway Gq
• (3) DG-PKC pathway Gq

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This receptor-G-protein complex is linked to and
activates phospholipase C, leading to an
increase in IP3 and DAG, which work together to
activate enzymes and to increase intracellular
calcium levels
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Click here to play the Membrane Bound
Receptors, G Proteins, and Calcium Channels Flash
Animation
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(4) G protein-ion channel pathway
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Binding of the ligand to the receptor alters the
receptors shape, which activates an associated
G-protein, which then activates effector
proteins, i.e., enzyme functions or ion channels
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The calcium-calmodulin system is similar to some
of the cAMP pathways, because it results in the
activation of protein kinases that can
phosphorylate key proteins required for
cellular responses
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The arachidonic acid cascade is activated in
inflammation responses cox inhibitors block
cyclooxygenase
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Not all responses to hydrophilic signals are
immediate
Increases in gene expression can occur, and
the resulting proteins can increase the
target cells response
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Eicosanoid A lipid mediator of inflammation
derived from the 20-carbon atom arachidonic acid
(20 in Greek is "eicosa") or a similar fatty
acid. The eicosanoids include the prostaglandins,
prostacyclin, thromboxane, and leukotrienes.
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Transmembrane signal transduction

• Mediated by G protein-linked receptor
• Mediated by enzyme-linked receptor
• Mediated by ion channel

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Binding of the ligand to the receptor alters the
receptors shape, which activates its enzyme
function, phosphorylating an intracellular
protein
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• (1) Tyrosine Kinase Receptor

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• Insulin receptor

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Growth factor receptor
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• Mitogen-activated protein kinase (MAPK) pathway

• PTK protein tyrosine kinase
• Ras G protein. It consists of an a subunit, b
  subunit, and g subunit
• MAPKKK MAPK kinase kinase
• MAPKK MAPK kinase
• MKP MAPK phosphatases
• TF tissue factor

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• (2) Receptor-associated tyrosine kinase

JAK stands for Janus kinase or Just Another
Kinase JAK2Tyrosine protein kinase 2
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Binding of the ligand to the receptor alters the
receptors shape, which activates an associated
enzyme function, phosphorylating an intracellular
protein
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• (3) Receptor guanylyl cyclase

Soluble GC
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Transmembrane signal transduction

• Mediated by G protein-linked receptor
• Mediated by enzyme-linked receptor
• Mediated by ion channel

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Binding of the ligand to the receptor alters the
receptors shape, which then opens (or closes)
an ion channel
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N2-ACh receptor channel
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Any other pathway else???
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Pheromone

• Pheromones are chemicals emitted by living
  organisms to send messages to individuals of the
  same species.

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• The male silk moth bombyx mori (Fig. 1, left) can
  detect very low quantities of the sex pheromone
  bombykol emitted by the female, and at the same
  time distinguishes bombykol from many other,
  often similar, volatile compounds in the air. A
  first step of olfaction is the tranfer of
  bombykol to the pheromone receptor at the
  neuronal membrane via the pheromone-binding
  protein (BmorPBP). Highly efficient uptake and
  release kinetics of bombykol at the pheromone
  binding protein is essential for olfactory
  function. However, BmorPBP features a central
  hydrophobic binding cavity for bombykol,
  completely encapsulating the ligand (Fig. 1,
  right) and the exit/entrance gate for bombykol is
  not known. Yet, the ligand has to enter and exit
  the cavity fast and reversibly.

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THANK YOU FOR YOUR ATTENTION!