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Signal transduction
Message converted from one form to another
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Hormones
Send a general communication throughout the body and are produced by endocrine cells
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Paracrine signals
- Signals diffuse locally through the extracellular fluid, and stay within the region from which they're secreted
- E.g. Inflammation on wounds
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Neuronal signaling
- Can travel long distance, but signal is picked up by individual cells through their own lines
- Delivered quickly and specifically to individual target cells through private lines
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Synapse
Junctions where electrical signals are converted to neurotransmitters which diffuse across the gap
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Contact-dependent
- Very short range and done through physical contact of signal molecules and receptors in plasma membrane
- In embryonic development, contact-dependent signals inhibit neighboring cells from becoming specialied in same way as cell signaling
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What happens when a signal molecule binds to its target?
It can alter the cell's shape, movement, metabolism, and gene expression
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What happens in the absence of cell signaling?
Most animal cells are programmed to kill themselves
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Signaling cascade
- Each target protein is activated by only one type of signal
- This receptor receives an external signal and generates a new intracellular signal in response
- This internal signal is passed on until a response is generated
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Functions of signaling cascades
- Transform, or transduce, the signal into a molecular form suitable for passing the signal along or stimulating a response
- They relay the signal from the point in the cell at which it is received to the point at which the response is produced
- Amplify the signal received, making it stronger
- Can distribute the signal to influence several processes in parallel
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Speed of a cell's response to a signal
- If acting on molecule already present in the cell, it will be quick
- If extracellular signals need changes in gene expression to make new proteins, it will take longer
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Which hormones can cross plasma membrane and bind to intracellular receptors?
- Large hydrophilic hormones cannot
- Small hydrophobic ones can (steroids)
- Binding of these small hydrophobic hormones to receptors in the cytosol or nucleus cause a large conformational change in their target proteins, that then either promote or inhibit gene transcription
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Which gasses can cross the plasma membrane?
- NO is a common gas that can diffuse (acts locally to vasodilate smooth muscle - vasodilate)
- Gases can alter conditions in seconds
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What does NO do in the cell?
- Binds and activates the enzyme guanylyl cyclase
- Stimulates the formation of cyclic GMP from the nucleotide GTP
- Cyclic GMP is the next signaling molecule in the chain, which leads to the cell response
- Local blood-vessel dilation occurs
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Viagra
Blocks the enzyme that degrades cyclic GMP, so the NO signal is maintained
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Functions of intracellular signaling pathways
- Relay signal onward, spreading it
- Amplify the signal, so few have a great affect
- Receive other signals from other pathways
- Distribute signal to other pathways
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Signaling proteins act as molecular switches
- Signal switches from active to inactive state
- If a signaling pathway is to recover after transmitting a signal and make itself ready to transmit another, every molecular switch must be reset to its original, unstimulated state
- For every activation mechanism there hase to be an inactivation mechanism
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Types of molecular switches
- Activated or deactivated by phosphorylation
- Protein kinase (adds phosphate group)
- Protein phosphatase (removes phosphate)
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GTP-binding proteins (G proteins and G-protein-coupled receptors)
- Switch between active or inactive form depending on if GTP (active) or GDP (inactive) is bound
- They can hydrolyze the GTP on their own because of their GTPase activity
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Ion-channel-coupled receptors
Opens ion channels and produces an electrical current
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G-protein coupled receptors
- Acive GTP-binding proteins
- Which then either activates an ezyme or ion channel
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Enzyme-coupled receptors (Cell surface receptor proteins)
- Act as enzymes or work with enzymes inside the cell
- Switching on this enzymatic activity then generates a hose of additional signals, including small molecules that are released into the cytosol
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Cell surface receptors can be acted upon by other molecules
- The natural ligand that is bound to the receptor can be mimicked by other molecules
- This ligand will either bind to the ligand-binding site or to another area on the receptor
- This will result in over-stimulating or blocking the receptor's activity
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Nicotine
- Acts on the neurotransmitter receptor in the central nervous system and muscle cells which are also acted upon by acetylcholine
- Enhancing effects of epi and norepi
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G-protein-coupled receptors
- Largest family of cell surface receptors
- Target for drug development (more than half of drugs work on GPCRs)
- Made of single protein chain
- Weaves back and forth between the plasma membrane 7 times
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G-protein-coupled receptors...
- Made of 3 subunits
- Attached by lipids to plasma membrane
- Unstimulated, GDP is bound to alpha subunit
- Stimulated, GTP is bound to alpha subunit
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Cholera toxin
- Binds to alpha subunit, and prevents the GTPase activity, therefore it stays activated much longer than it should
- Causes prolonged release of Cl- and H2O
- Can be deathly diarrhea and dehydration
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G proteins regulate ion channels
- Heartbeat regulated by 2 sets of nerves (1 speeds and 1 slows)
- Nerves that signal slowing releases acetylcholine
- By complex will o pen the K+ channels, and K+ flows out and inhibits the heart cells excitability
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Two most common target enzymes for G proteins
- Adenylyl cyclase (involved in making cyclic AMP)
- Phospholipase C (inositol triphosphate and diacylglycerol)
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Cyclic AMP
- Activated adenylyl cyclase catalyzes the synthesis of cyclic AMP from ATP
- Cyclic AMP activates cyclic-AMP-dependent protein kinase (PKA)
- Activated PKA catalyzes phosphorylation of serines or proteins
- Adrenaline signal ultimately causes the breakdown of glycogen in skeletal muscles
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Inositol phospholipid pathway
- Triggers increase in Ca++
- Activated phospholipase C removes the sugar-phosphate head it creates 2 signaling molecules: inositl 1,4,5-triphosphate (IP3) and diacylglycerol (DAG)
- IP3 remains in cytosol
- DAG stays in plasma membrane
- IP3 opens Ca++ channels of ER and Ca++ increases in cytosol
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More on inositol phospholipid pathway
IP3 released into the cytosol will eventually encounter endoplasmic reticulum; there it binds to and opens Ca++ channels that are embedded in the endoplasmic reticulum membrane
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