Post on 18-Dec-2015
Cell Cell Communication-ICommunication-I
Pin Ling ( 凌 斌 ), Ph.D.
Department of Microbiology & Immunology, NCKU
ext 5632; lingpin@mail.ncku.edu.tw
Reference:
“Mechanisms of Cell Communication”, The Cell (5th edition), Chapter 15
Outline General principles of cell communication
Signaling through G-protein-coupled cell surface receptors (GPCRs) and small intracellular mediators
Signaling through enzyme-coupled cell-surface receptors
Signaling pathways dependent on regulated proteolysis of latent gene regulatory proteins
Signaling in plants
Your involvement is the key to success in this lecture.
Features of Cell CommunicationFeatures of Cell Communication
1. A single host cell (E. Coli) or multicellular organisms need to communicate with environmental cues (stimuli), then leading to appropriate responses.
2. How to do “Communication” with environmental cues?=> Signaling Transduction
What is Signaling Transduction?What is Signaling Transduction?
• Conversion of a signal from one physical or chemical form into another.
• The process initiated by recognition a Signal by a Sensor (receptor, kinase or enzyme) in the cell, then converting to one or more cellular responses through a series of signal
transmission.
Inputs
Responses
Signals
Cellular Responses (Proliferation, Differentiation, & Apoptosis)
Signaling Cascades Cell
Signaling Transduction Regulates Cellular Responses
Human
ReceptorsReceptors
Signal Signal TransduceTransduce
rsrs
EffectorsEffectors
A simple scheme of signal A simple scheme of signal transductiontransduction
Molecules involved in this process,
called Signaling Molecules
Figure 15-2 Molecular Biology of the Cell (© Garland Science 2008)
Budding yeast cells responding Budding yeast cells responding to to a mating factor (Pheromone)a mating factor (Pheromone)
Budding yeast
Features of Cell Features of Cell Communication-ICommunication-I
1. Signal molecules bind to surface or intracellular receptors.
2. There are four types of cellular signaling: (1) Cell contact, (2) Paracrine, (3) Synaptic, and (4) Endocrine.
3. Extracellular signal molecules can act over short or
long distance.
4. Extracellular signals can act slowly or rapidly to change the behavior of a target cell.
Cell surface vs intracellular Cell surface vs intracellular receptorsreceptors
Four types of intercellular Four types of intercellular signalingsignaling
Signaling via gap junctions Signaling via gap junctions
Strategies for long-range Strategies for long-range signalingsignaling
Early vs later responses to Early vs later responses to extracellular signals extracellular signals
Features of Cell Features of Cell Communication-IICommunication-II
1. Each cell is programmed to respond to the combinations of extracellular signal molecules.
2. Different cell types respond differently to the same extracellular signal molecules.
3. The same cell type can act differently depending upon signal concentration.
4. Examples of intracellular signaling, e.g. NO signaling, Nuclear receptor signaling.
Combinations of total Combinations of total signals decide the cell fatesignals decide the cell fate
Various cellular Various cellular responses induced by responses induced by
acetylcholineacetylcholine
The same cell type can act The same cell type can act differently upon signal differently upon signal
concentrationconcentration
NO functions in smooth NO functions in smooth muscle relaxationmuscle relaxation
Steroid hormones & other Steroid hormones & other non-gaseous signal non-gaseous signal
molecules molecules
The Nuclear Receptor FamilyThe Nuclear Receptor Family
Activation of nuclear Activation of nuclear receptors by ligand bindingreceptors by ligand binding
Primary & secondary Primary & secondary responses by nuclear responses by nuclear
receptorsreceptors
Outline General principles of cell communication
Signaling through G-protein-coupled cell surface receptors (GPCRs) and small intracellular mediators
Signaling through enzyme-coupled cell-surface receptors
Signaling pathways dependent on regulated proteolysis of latent gene regulatory proteins
Signaling in plants
Three classes of cell surface Three classes of cell surface receptorsreceptors
Three classes of cell surface Three classes of cell surface receptorsreceptors
Features of intracellular Features of intracellular signaling pathways-I signaling pathways-I
1. Small intracellular signaling molecules => 2nd messengers, e.g. Ca2+, cAMP, or Diacylglycerol (DAG).
2. Large intracellular signaling molecules => Signaling proteins
3. Signaling proteins act as “Molecular Switches” regulated by post-translational modifications (PTMs).
4. Signaling complex formation enhances the efficiency & specificity of the response.
5. Modular interaction domains mediate interactions between signaling proteins
A A Signaling Signaling cascade: A cascade: A surface surface receptor to receptor to the the nucleusnucleus
Molecular Switches: Molecular Switches:
Post-Translational Post-Translational ModificationsModifications
Signal IntegrationSignal Integration
Signaling complex formation Signaling complex formation by a scaffold proteinby a scaffold protein
Signaling complex formation Signaling complex formation by by
an activated receptoran activated receptor
Signaling complex formation Signaling complex formation on phosphoinositoide on phosphoinositoide
docking sites docking sites
Signaling complex formation Signaling complex formation usingusing
modular interaction domains modular interaction domains
Features of intracellular Features of intracellular signaling pathways-II signaling pathways-II
1. Cells can respond abruptly or gradually to an increasing signal.
2. Intracellular signaling networks use feedback loops to regulate the process.
3. Cells can adjust their sensitivity to a signal.
Smoothly graded vs Smoothly graded vs switchlike signaling switchlike signaling
responses-Iresponses-I
Smoothly graded vs Smoothly graded vs switchlike signaling switchlike signaling
responses-IIresponses-II
Activation curves for an allosteric Activation curves for an allosteric protein by various effector protein by various effector concentrationsconcentrations
A positive vs negative A positive vs negative feedback loopfeedback loop
Positive vs negative Positive vs negative feedback loopfeedback loop
An example of An example of a positive a positive feedback loopfeedback loop
Many ways to become Many ways to become desensitized (adapted) to a desensitized (adapted) to a
signalsignal
Outline General principles of cell communication
Signaling through G-protein-coupled cell surface receptors (GPCRs) and small intracellular mediators
Signaling through enzyme-coupled cell-surface receptors
Signaling pathways dependent on regulated proteolysis of latent gene regulatory proteins
Signaling in plants
Signaling through G-protein-Signaling through G-protein-coupled cell surface receptors coupled cell surface receptors
(GPCRs)-I(GPCRs)-I1. GPCRs are the largest family of cell-surface
receptors (700 GRCRs in human). They mediate our sense of sight, smell, and taste.
2. Extracellular signaling molecules acting on GPCRs are varied in structure, including hormones, lipid mediators, & neurotransmitters.
3. All GPCRs have a common structure- a seven transmembrane peptide
4. All GPCRs use G proteins to relay the signal into the cell.
Signaling through G-protein-Signaling through G-protein-coupled cell surface receptors coupled cell surface receptors
(GPCRs)-II(GPCRs)-II5. Some G proteins regulate the production of
cyclic AMP.
6. Some G proteins activate an inosital phospholipid signaling pathway via Phospholipase C-beta (PLC-b).
GPCRs and G ProteinGPCRs and G Protein
GPCR
G Protein: subunit: GTPase subunit & subunit
Activation of Activation of GPCRs & GPCRs &
G ProteinG Protein
cAMP links some GPCR cAMP links some GPCR signals to gene expressionsignals to gene expression
Some hormones act GPCR Some hormones act GPCR via cAMPvia cAMP
Activation of cAMP-dep Activation of cAMP-dep protein kinase (PKA)protein kinase (PKA)
Some GPCRs activate PKC Some GPCRs activate PKC and cytosolic Caand cytosolic Ca2+2+
CaCa2+2+-mediated intracellular -mediated intracellular SignalingSignaling
1. Ca2+ functions as an intracellular mediator.
2. Ca2+ enter the cytosol from outside through various Ca2+ ion channel.
3. Ca2+ from the ER enter the cytosol through IP3
receptors or ryanodine receptors.
4. Several mechanisms keep Ca2+ in the cytosol low in resting cells.
5. Ca2+ oscillations affect a cell response.
6. Ca2+/Calmodulin-dep protein kinase mediate cellular responses (learning & memory in the nervous system).
Ca2+ functions as an Ca2+ functions as an intracellular mediatorintracellular mediator
Multiple ways to keep Ca2+ Multiple ways to keep Ca2+ low in the cytosollow in the cytosol
Vasopressin-induced Ca2+ Vasopressin-induced Ca2+ oscillations in a liver celloscillations in a liver cell
Vasopressin
GPCR
PLC-
Ca2+ oscillations
Activation of CaM-kinase IIActivation of CaM-kinase II
CaM-kinase II as a CaM-kinase II as a frequency decoder of Ca2+ frequency decoder of Ca2+
oscillationsoscillations
Smell &vision depend on Smell &vision depend on GPCRsGPCRs
A rod photoreceptor cell & A rod photoreceptor cell & its response to lightits response to light
A rod A rod photoreceptor photoreceptor cell & its cell & its response response
to lightto light
Four major families of Four major families of trimeric G proteinstrimeric G proteins
GPCR desensitization GPCR desensitization depends on receptor depends on receptor
phosphorylationphosphorylation
““Cell Communication Cell Communication II” to be continuedII” to be continued
Figure 15-47 Molecular Biology of the Cell (© Garland Science 2008)