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@@ -25,25 +25,9 @@ What types of cell-cell communication underly signaling? The answer is familiar
--- ---
## Endocrine signaling ## Synaptic, paracrine, and endocrine signaling
<div><img src="tmp/img002_91bc4ab.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.01-2R_copy_eef31ad.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 7.1</figcaption></figure>
Note:
---
## Paracrine signaling
<div><img src="tmp/img003_d18bced.jpg" height="100px"><figcaption></figcaption></div>
Note:
---
## Signaling by membrane proteins
<div><img src="tmp/img005_64aadb9.jpg" height="100px"><figcaption></figcaption></div>
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@@ -61,7 +45,6 @@ Note:
Note: Note:
--- ---
## Signal amplification ## Signal amplification
@@ -69,7 +52,8 @@ Note:
* results in a tremendous increase in the potency of the initial signal * results in a tremendous increase in the potency of the initial signal
* permits precise control of cell behavior * permits precise control of cell behavior
<div><img src="tmp/Neuroscience5e-Fig-07.02-0_bed2f4c.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.02-0_87ce39a.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 7.2</figcaption></figure>
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@@ -77,11 +61,16 @@ Note:
## Types of receptors ## Types of receptors
<div style="font-size:0.8em;">
<div></div>
* Ligand gated ion channels (channel linked receptors/ionotropic receptors)– e.g. nAChR, AMPA receptors * Ligand gated ion channels (channel linked receptors/ionotropic receptors)– e.g. nAChR, AMPA receptors
* Enzyme linked receptors– typically have extracellular binding site for signals. Has intracellular domain with catalytic activity regulated by signal. Most are protein kinases that phosphorylate intracellular proteins. e.g. tyrosine kinase * Enzyme linked receptors– typically have extracellular binding site for signals. Has intracellular domain with catalytic activity regulated by signal. Most are protein kinases that phosphorylate intracellular proteins. e.g. tyrosine kinase
* G-protein coupled receptors– 7-transmembrane spanning receptors that signal through trimeric G-proteins intracellularly. The proteins can alter the function of many downstream proteins. e.g. muscarinic AChR, metabotropic glutamate receptors * G-protein coupled receptors– 7-transmembrane spanning receptors that signal through trimeric G-proteins intracellularly. The proteins can alter the function of many downstream proteins. e.g. muscarinic AChR, metabotropic glutamate receptors
* Intracellular receptors– activated by cell permeant or lipophilic signaling molecules like steroid hormones. Signal binds directly to an intracellular protein which then activates transcription * Intracellular receptors– activated by cell permeant or lipophilic signaling molecules like steroid hormones. Signal binds directly to an intracellular protein which then activates transcription
</div>
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@@ -90,9 +79,8 @@ Note:
## Categories of cellular receptors ## Categories of cellular receptors
Neuroscience 5e 7.4 <figure><img src="figs/Neuroscience5e-Fig-07.04-0R_1_631f6c3.png" height="400px"><figcaption>Neuroscience 5e Fig. 7.4</figcaption></figure>
<div><img src="tmp/Neuroscience5e-Fig-07.04-0R_f4a3cfb.jpg" height="100px"><figcaption></figcaption></div>
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@@ -104,7 +92,8 @@ For enzyme linked receptors the signal binds extracellularly, which activates th
## Categories of cellular receptors ## Categories of cellular receptors
Neuroscience 5e 7.4 <figure><img src="figs/Neuroscience5e-Fig-07.04-0R_2_c164eb9.png" height="400px"><figcaption>Neuroscience 5e Fig. 7.4</figcaption></figure>
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@@ -122,7 +111,7 @@ For intracellular receptors, the signaling molecule passes through lipid membran
* Two types of G-proteins: * Two types of G-proteins:
* Heterotrimeric G- proteins, composed of an α,β, γ subunits. Multiple members of each class. α subunit binds and hydrolyses GTP * Heterotrimeric G- proteins, composed of an α,β, γ subunits. Multiple members of each class. α subunit binds and hydrolyses GTP
* Small G-proteins– monomeric GTPases (e.g. ras) * Small G-proteins– monomeric GTPases (e.g. ras)
* Active when bound to GTP, inactive when bound to GDP. * Active when bound to GTP, inactive when bound to GDP
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@@ -148,12 +137,12 @@ Rate of GTP hydrolysis is important property of G-protein mediated signaling and
## Types of GTP-binding proteins ## Types of GTP-binding proteins
<div><img src="tmp/Neuroscience5e-Fig-07.05-0_79ccd4d.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.05-0_ae701d1.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 7.5</figcaption></figure>
Note: Note:
--- ---
## Trimeric G-protein signaling ## Trimeric G-protein signaling
@@ -164,7 +153,8 @@ Note:
* Dissociates complex and activates * Dissociates complex and activates
* α and βγ subunits * α and βγ subunits
<div><img src="tmp/image_ed5b758.png" height="100px"><figcaption></figcaption></div> <figure><img src="figs/MolBiolCell-4e-Fig-15-28_bb1fb6c.png" height="300px"><figcaption>Molecular Biology of the Cell 4e Fig. 15.28</figcaption></figure>
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@@ -190,11 +180,11 @@ Effector enzymes for activated G-proteins include adenylyl cyclase, guanylyl cyc
## Effector pathways associated with G-protein coupled receptors ## Effector pathways associated with G-protein coupled receptors
<div><img src="tmp/Neuroscience5e-Fig-07.06-0_0622e51.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.06-0_c5e7495.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 7.6</figcaption></figure>
Note: Note:
There are many types of alpha, beta, and gamma g-protein subunits allowing a specific and diverse range of downstream responses. There are many types of alpha, beta, and gamma g-protein subunits allowing a specific and diverse range of downstream responses.
This shows three examples of different heterotrimeric g proteins bound to 3 types of receptors with 3 different cellular responses. This shows three examples of different heterotrimeric g proteins bound to 3 types of receptors with 3 different cellular responses.
@@ -221,7 +211,8 @@ One target of calcium is calmodulin, a calcium binding protein abundant in the c
## Proteins involved in delivering and removing calcium to the cytoplasm ## Proteins involved in delivering and removing calcium to the cytoplasm
<div><img src="tmp/Neuroscience5e-Fig-07.07-2R_e19682f.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.07-2R_copy_3559450.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 7.7</figcaption></figure>
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@@ -244,41 +235,37 @@ Another one intracellular releasing channel is the ryanodine receptor. These are
## Calcium activates calmodulin ## Calcium activates calmodulin
<div><img src="tmp/image1_ee185b5.png" height="100px"><figcaption></figcaption></div> <figure><img src="figs/MolBiolCell-4e-Fig-15-40_8aee979.png" height="400px"><figcaption>Molecular Biology of the Cell 4e Fig. 15.40</figcaption></figure>
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--- ---
## Title Text ## Calcium second messaging video summary
[http://courses.pbsci.ucsc.edu/mcdb/bio125/Animation07-02CalciumasaSecondMessenger.mov](http://courses.pbsci.ucsc.edu/mcdb/bio125/Animation07-02CalciumasaSecondMessenger.mov) <div><video height=400px controls src="figs/Animation07-02CalciumasaSecondMessenger.mp4"></video><figcaption>Neuroscience 5e Animation 7.2</figcaption></div>
<div><img src="tmp/posterImage_aefb8c9.png" height="100px"><figcaption></figcaption></div>
Note: Note:
--- ---
## Second messengers: cyclic nucleotides ## Second messengers: cyclic nucleotides
* cAMP and cGMP– derivatives of ATP and GTP. Made by adenylyl cyclase and guanylyl cyclase * cAMP and cGMP– derivatives of ATP and GTP. Made by adenylyl cyclase and guanylyl cyclase
* Bind to many targets– cAMP to protein kinase A; cGMP to protein kinase G * Bind to many targets– cAMP to protein kinase A, cGMP to protein kinase G
* Phosphodiesterases cleave cAMP and cGMP to inactivate them * Phosphodiesterases cleave cAMP and cGMP to inactivate them
Note: Note:
--- ---
## cAMP formation and destruction ## cAMP formation and destruction
<div><img src="tmp/image2_cd109cb.png" height="100px"><figcaption></figcaption></div> <figure><img src="figs/MolBiolCell-4e-Fig-15-31_f75639e.png" height="300px"><figcaption>Molecular Biology of the Cell 4e Fig. 15.31</figcaption></figure>
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@@ -300,18 +287,20 @@ Note:
## Diacylglycerol and IP3 ## Diacylglycerol and IP3
<div><img src="tmp/image3_ff001a8.png" height="100px"><figcaption></figcaption></div> <figure><img src="figs/MolBiolCell-4e-Fig-15-35_466d627.png" height="400px"><figcaption>Molecular Biology of the Cell 4e Fig. 15.35</figcaption></figure>
Note: Note:
Phosphatidylinositol 4,5-bisphosphate: PIP2, Phosphatidylinositol 4,5-bisphosphate: PIP2
--- ---
## Neuronal second messengers ## Neuronal second messengers
<div><img src="tmp/Neuroscience5e-Fig-07.07-1R_075e716.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.07-1R_copy_20bca17.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 7.7</figcaption></figure>
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@@ -322,36 +311,16 @@ This table summarizes neuronal second messengers, their sources, targets, and in
## Second messenger life cycles ## Second messenger life cycles
cyclic nucleotides <div><figcaption class="big">cyclic nucleotides</figcaption><img src="figs/Neuroscience5e-Fig-07.07-3R_copy_b4b6941.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 7.7</figcaption></div>
lipid signals <div><figcaption class="big">lipid signals</figcaption><img src="figs/Neuroscience5e-Fig-07.07-4R_copy_724e472.jpg" height="200px"><figcaption>Neuroscience 5e Fig. 7.7</figcaption></div>
Neuroscience 5e 7.7
<div><img src="tmp/Neuroscience5e-Fig-07.07-3R_3c25bf5.jpg" height="100px"><figcaption></figcaption></div>
<div><img src="tmp/Neuroscience5e-Fig-07.07-4R_d7c0fa2.jpg" height="100px"><figcaption></figcaption></div>
Note: Note:
And this depicts the mechanisms involved in production and degradation or removal of cyclic nucleotides and DAG and IP3. And this depicts the mechanisms involved in production and degradation or removal of cyclic nucleotides and DAG and IP3.
---
## Second messenger life cycles
cyclic nucleotides
lipid signals
gas signals
<div><img src="tmp/PN08073_69fa3e7.jpg" height="100px"><figcaption></figcaption></div>
Note:
--- ---
## 2nd messengers target protein kinases and phosphatases ## 2nd messengers target protein kinases and phosphatases
@@ -377,7 +346,8 @@ Protein substrates of kinases and phosphataes include enzymes, neurotransmitter
## Regulation of cellular proteins by phosphorylation ## Regulation of cellular proteins by phosphorylation
<div><img src="tmp/Neuroscience5e-Fig-07.08-0_3d12fd1.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.08-0_fe35b8f.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 7.8</figcaption></figure>
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@@ -399,19 +369,10 @@ Note:
## Mechanism of activation of protein kinases ## Mechanism of activation of protein kinases
binding of cAMP to regulatory <figure style="margin:15px 0;"><figcaption class="big">binding of cAMP to regulatory subunits free up the catalytic subunits</figcaption><img src="figs/Neuroscience5e-Fig-07.09-1R_copy_9cfd048.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 7.9</figcaption></figure>
<figure style="margin:15px 0;"><figcaption class="big">binding of calmodulin opens up protein to activate catalytic domain</figcaption><img src="figs/Neuroscience5e-Fig-07.09-2R_copy_d343a3d.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 7.9</figcaption></figure>
<figure style="margin:15px 0;"><figcaption class="big">DAG causes PKC to change its localization which leads it to be active</figcaption><img src="figs/Neuroscience5e-Fig-07.09-3R_copy_e5e5f7e.jpg" height="100px"><figcaption>Neuroscience 5e Fig. 7.9</figcaption></figure>
subunits free up the catalytic subunits
binding of calmodulin opens up
protein to activate catalytic domain
DAG causes PKC to change its
localization which leads it to be active
<div><img src="tmp/Neuroscience5e-Fig-07.09-0_630932e.jpg" height="100px"><figcaption></figcaption></div>
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@@ -421,12 +382,12 @@ Note:
## Protein kinase A activation ## Protein kinase A activation
<div><img src="tmp/image4_632667b.png" height="100px"><figcaption></figcaption></div> <figure><img src="figs/MolBiolCell-4e-Fig-15-32_607bbe8.png" height="300px"><figcaption>Molecular Biology of the Cell 4e Fig. 15.32</figcaption></figure>
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--- ---
## Other kinases ## Other kinases
@@ -449,7 +410,7 @@ Mitogen activated protein kinases (MAP kinases)
## MAP kinase cascade ## MAP kinase cascade
<div><img src="tmp/image5_ad676a6.png" height="100px"><figcaption></figcaption></div> <figure><img src="figs/MolBiolCell-4e-Fig-15-56_d3306b4.png" height="300px"><figcaption>Molecular Biology of the Cell 4e Fig. 15-56</figcaption></figure>
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@@ -474,7 +435,7 @@ CREB is an important nuclear signal
## Steps involved in transcription of DNA to RNA ## Steps involved in transcription of DNA to RNA
<div><img src="tmp/Neuroscience5e-Fig-07.10-0_4962198.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.10-0_9a72f7c.jpg" height="500px"><figcaption>Neuroscience 5e Fig. 7.10</figcaption></figure>
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@@ -485,10 +446,8 @@ uas: upstream activator sequence
>upstream activating sequence or upstream activation sequence (UAS) is a cis-acting regulatory sequence. It is distinct from the promoter and increases the expression of a neighbouring gene. >upstream activating sequence or upstream activation sequence (UAS) is a cis-acting regulatory sequence. It is distinct from the promoter and increases the expression of a neighbouring gene.
-upstream from minimal promoter TATA box, binding site for transactivators -upstream from minimal promoter TATA box, binding site for transactivators
-a cis acting regulatory sequence (like IRES) -a cis acting regulatory sequence (like IRES)
--- ---
## CREB ## CREB
@@ -503,54 +462,27 @@ Note:
## Transcriptional regulation by CREB ## Transcriptional regulation by CREB
<div><img src="tmp/Neuroscience5e-Fig-07.11-0_2eaee54.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.11-0_22d362e.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 7.11</figcaption></figure>
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--- ---
## Title Text ## Chemical signaling mechanisms video summary
[http://courses.pbsci.ucsc.edu/mcdb/bio125/Animation07-01ChemicalSignalingMechanismsandAmplification.mov](http://courses.pbsci.ucsc.edu/mcdb/bio125/Animation07-01ChemicalSignalingMechanismsandAmplification.mov) <div><video height=400px controls src="figs/Animation07-01ChemicalSignalingMechanismsandAmplification.mp4"></video><figcaption>Neuroscience 5e Animation 5.2</figcaption></div>
<div><img src="tmp/posterImage1_eb3dd6e.png" height="100px"><figcaption></figcaption></div>
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---
## Nurturing defects in CREB mutant mice
WT
mutant
<div><img src="tmp/image6_f94d96e.png" height="100px"><figcaption></figcaption></div>
Note:
---
## How does NGF promote axon outgrowth
-NGF
+NGF
<div><img src="tmp/image7_7dc0be2.png" height="100px"><figcaption></figcaption></div>
Note:
--- ---
## Mechanism of action of NGF ## Mechanism of action of NGF
<div><img src="tmp/Neuroscience5e-Fig-07.12-0_968df2f.jpg" height="100px"><figcaption></figcaption></div> <figure><img src="figs/Neuroscience5e-Fig-07.12-0_1bc4863.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 7.12</figcaption></figure>
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@@ -561,12 +493,18 @@ nerve growth factor, binds to tyrosine kinase receptor (TrkA) leading to…
## Signaling at cerebellar parallel fiber synapses ## Signaling at cerebellar parallel fiber synapses
<div style="font-size:0.7em;width:400px;">
<div></div>
* Glutamate released from presynaptic cell binds ionotropic and metabotropic glutamate receptors * Glutamate released from presynaptic cell binds ionotropic and metabotropic glutamate receptors
* AMPA receptor opens and excites cell * AMPA receptor opens and excites cell
* mGluR receptor activates a signal transduction pathway that feeds back and decreases AMPA receptor activity * mGluR receptor activates a signal transduction pathway that feeds back and decreases AMPA receptor activity
* Called long term depression because now the same stimulus will lead to less depolarization than before (weakened synapse) * Called long term depression because now the same stimulus will lead to less depolarization than before (weakened synapse)
<div><img src="tmp/Neuroscience5e-Fig-07.13-0_843784b.jpg" height="100px"><figcaption></figcaption></div> </div>
<div style="margin:0 15px;"><img src="figs/Neuroscience5e-Fig-07.13-0_0ff2e8b.jpg" height="300px"><figcaption>Neuroscience 5e Fig. 7.13</figcaption></div>
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@@ -586,6 +524,9 @@ likely from phosphorylation of AMPA receptors by PKC and their elimination from
## Regulation of tyrosine hydroxylase by protein phosphorylation ## Regulation of tyrosine hydroxylase by protein phosphorylation
<div style="font-size:0.7em;">
<div></div>
* AP invades axon terminal * AP invades axon terminal
* Voltage-gated Ca²⁺ channels open * Voltage-gated Ca²⁺ channels open
* Intracellular Ca²⁺ does two things: * Intracellular Ca²⁺ does two things:
@@ -597,7 +538,10 @@ likely from phosphorylation of AMPA receptors by PKC and their elimination from
* Increase in transmitter release * Increase in transmitter release
* Increase in post-synaptic response * Increase in post-synaptic response
<div><img src="tmp/Neuroscience5e-Fig-07.14-0_5f1370f.jpg" height="100px"><figcaption></figcaption></div> </div>
<div style="margin:0 15px;"><img src="figs/Neuroscience5e-Fig-07.14-0_6a79350.jpg" height="400px"><figcaption>Neuroscience 5e Fig. 7.14</figcaption></div>
Note: Note: