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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>
Note:
---
## Paracrine signaling
<div><img src="tmp/img003_d18bced.jpg" height="100px"><figcaption></figcaption></div>
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---
## Signaling by membrane proteins
<div><img src="tmp/img005_64aadb9.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>
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@@ -61,7 +45,6 @@ Note:
Note:
---
## Signal amplification
@@ -69,7 +52,8 @@ Note:
* results in a tremendous increase in the potency of the initial signal
* 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
<div style="font-size:0.8em;">
<div></div>
* 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
* 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
</div>
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@@ -90,9 +79,8 @@ Note:
## 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
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:
* 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)
* 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
<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:
---
## Trimeric G-protein signaling
@@ -164,7 +153,8 @@ Note:
* Dissociates complex and activates
* 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
<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:
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.
@@ -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
<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
<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>
Note:
---
## 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><img src="tmp/posterImage_aefb8c9.png" height="100px"><figcaption></figcaption></div>
<div><video height=400px controls src="figs/Animation07-02CalciumasaSecondMessenger.mp4"></video><figcaption>Neuroscience 5e Animation 7.2</figcaption></div>
Note:
---
## Second messengers: cyclic nucleotides
* 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
Note:
---
## 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
<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:
Phosphatidylinositol 4,5-bisphosphate: PIP2,
Phosphatidylinositol 4,5-bisphosphate: PIP2
---
## 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
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:
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
@@ -377,7 +346,8 @@ Protein substrates of kinases and phosphataes include enzymes, neurotransmitter
## 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
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
<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>
Note:
---
## Other kinases
@@ -449,7 +410,7 @@ Mitogen activated protein kinases (MAP kinases)
## 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
<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 from minimal promoter TATA box, binding site for transactivators
-a cis acting regulatory sequence (like IRES)
---
## CREB
@@ -503,54 +462,27 @@ Note:
## 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>
Note:
---
## 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><img src="tmp/posterImage1_eb3dd6e.png" height="100px"><figcaption></figcaption></div>
<div><video height=400px controls src="figs/Animation07-01ChemicalSignalingMechanismsandAmplification.mp4"></video><figcaption>Neuroscience 5e Animation 5.2</figcaption></div>
Note:
---
## 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
<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
<div style="font-size:0.7em;width:400px;">
<div></div>
* Glutamate released from presynaptic cell binds ionotropic and metabotropic glutamate receptors
* AMPA receptor opens and excites cell
* 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)
<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
<div style="font-size:0.7em;">
<div></div>
* AP invades axon terminal
* Voltage-gated Ca²⁺ channels open
* 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 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>
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