Chapter 11: Cell Communication Word Roots: liga- = bound or tied to trans- = across Ligand – a...
Transcript of Chapter 11: Cell Communication Word Roots: liga- = bound or tied to trans- = across Ligand – a...
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Chapter 11: Cell Communication
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Word Roots:
liga- = bound or tied to
trans- = across
Ligand – a small molecule that specifically binds to a larger one.
Transduction – the transmission of external signals and conversion of a message inside of the cell
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Signal Transduction Pathways•Local Signaling
•Direct contact
•Cell junctions
•Local Regulators
•Paracrine signaling
•Synaptic signaling
•Long Distance Signaling
•Hormones
•Nervous
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Direct Contact
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Evolution of Cell Signaling• Yeast cells
– Identify their mates by cell signaling
factorReceptor
Exchange of mating factors. Each cell type secretes a mating factor that binds to receptors on the other cell type.
1
Mating. Binding of the factors to receptors induces changes in the cells that lead to their fusion.
New a/ cell. The nucleus of the fused cell includes all the genes from the a and a cells.
2
3
factorYeast cell,mating type a
Yeast cell,mating type
a/
a
a
Figure 11.2
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Local Signaling
•Less specific
•Growth factors
•More Specific
•Neurotransmitters
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Long Distance Signaling •Very Specific
•Target specific cells
•Hormones (endocrine signaling)
•Nerves – electrical transmission of impulses
www.arikah.com
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Three Stages of Cell Signaling•Earl W. Sutherland – 1971
•Signal Transduction Pathway for glycogen breakdown.
•Reception
•Target cell detects a signal molecule from outside the cell when a ligand binds to a receptor
•Transduction
• binding of signal molecule changes the shape of the receptor initiating transduction sequence of changes in a series of molecules
•Response
•Transduced signal triggers a specific cellular response
•Ex: catalysis of enzyme, activation of genes, etc..
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http://pizaroscience.weebly.com/uploads/2/0/4/6/20462914/11_05cellsignaling_a.mpg
Three Stages of Cell Signaling
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Step 1: Reception•Receptor Protein (conformational change)
•Membrane
•Cytoplasm
•Nucleus
•Signal Molecule
•Ligand (highly specific)
•Small/hydrophobic
•Ex: steroid hormones
•Large/water soluble
•Ex: epinepherine
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http://highered.mheducation.com/sites/9834092339/student_view0/chapter9/mechanism_of_action_of_lipid-soluble_messengers.html
A hydrophobic ligand can readily cross the plasma membrane and bind to an intracellular receptor
Testosterone acts as a transcription factor
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Three Main Types of Plasma Membrane Receptors
•G-Protein Linked
•Receptor Tyrosine Kinases
•Ion Channel
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http://learn.genetics.utah.edu/content/cells/cellcom/
G-Protein Linked
Ex: Fight or Flight Response
Reception: Epinepherine targets liver and muscle cells
Transduction: activates glycogen phosphorylase
Response: break down glycogen into glucose
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G-Protein Linked•Embryonic development, sensory reception, yeast mating factors, epinepherine, many other hormones and neurotransmitters
•GTP – guanosine triphosphate (a nucleiotide)
Inactive G protein Ligand binding receptor shape change inactive G protein binds GTP replaces GDP activating the G protein
Activated G protein dissociates from the receptor binds to an enzyme and alters its activity triggering the next step in the pathway
G protein acts as GTPase hydrolyzing GTP into inactive GDP shutting down pathway when ligan is not present
GTP
Adenylyl cyclase
GDP
GDP Pi
GTP
Signal transduction pathway initiated
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Receptor Tyrosine Kinases •Kinase – enzyme that catalyzes the transfer of a phosphate group
•Tyrosine kinase – membrane receptors that attach phosphates to the amino acid, tyrosine
•Regulates growth and reproduction
•Multiple pathways stimulated
•Branched pathways (10+)
•Abnormal receptor tyrosine kinases may contribute to some kinds of cancer
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Receptor Tyrosine Kinases
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Ion Channel Receptors•Ligand-gated ion channels
•Nervous system
•Sodium –Potassium Pump
•Some channels are controlled by electrical signals instead of a ligand
•Na+ and Ca2+
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Sodium Potassium Pump
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Checkpoint
• Compare and contrast the three major types of membrane receptors.
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Step 2: Transduction•Multi-step
•Amplifies signal – signal sent to multiple molecules
•Require Relay Molecules
•Protein Kinases – transfers phosphate groups from ATP to a protein
•Serine/threonine kinases (animals, plants, fungi)
•Phosphorylation cascade
•Conformational change
•Increase or decrease activity of the protein
•Protein Phosphatases – remove phosphates from proteins
•Recycle and reuse kinases (dephosphorylation)
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Reception
Transduction
ResponsePhosphorylation Cascade
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Second Messengers•Small, non-protein, water soluble molecules or ions
•Diffuse easily
•Easily Amplified
•Cyclic AMP (cAMP)
•Calcium ions (Ca2+)
•Inositol triphosphate (IP3)
•Diacylglycerol (DAG)
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Cyclic AMP•Cyclic adenosine monophosphate
•Created by Adenylyl Cyclase from ATP
•Many cAMP molecules – amplification
•Phosphodiesterase
•Activates Protein Kinase A
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‘Locking’ the pathway
Cholera – Vibrio cholerae
Locks G-Protein for water and salt regulation ‘on’
Unable to hydrolyze GTP into GDP = stuck in active form
Diarrhea
Vasodilatation
Cyclic GMP – relaxes artery walls
Viagra – blocks cyclic cGMP from breaking down into GMP
– increases blood flow, prolonging the signal
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Calcium Ions and Inositol Triphosphate•Ca2+ low in cytosol, high in ER and ECF
•Active transport and membrane proteins
•Controlled by gated ion channels
•Regulates:
•Muscle contraction
•Secretion of other substances
•Cell division
•Used:
•G-protein
•Receptor Tyrosine Kinases
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Step 3: Response•Cytoplasmic or Nuclear
•Regulates:
•Enzyme/Protein activity
•Enzyme/Protein creation
•Transcription factors
•Growth factors
•Hormones
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Cytoplasmic Response
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Nuclear Response
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Benefits of Transduction Pathways•Signal Amplification
•Each step – more amplification
•Specificity
•Branched pathways – Receptor Tyrosine Kinases
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Signaling Efficiency•Scaffolding Proteins
•Signaling Complexes
•Proteins can participate in:
•More than one pathway in 1 cell
•Many pathways in different cells
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Step 4: Signal Termination•Reversible binding
•Signal molecule unbinds
•GTPase activity
•Phosphodiesterase
•Phosphatases