This is my notes which I wrote as I was taking a video lecture
which is originated from
https://www.youtube.com/watch?v=-qMSF0pz1bA&list=PLWEQK2NI_UhL5cT7AcvGYknIEkazdTVQw
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Endoplasmic reticulum has 2 kinds:
Smooth Endoplasmic reticulum
Rough Endoplasmic reticulum
Center circle shape: nuclei
Object around nuclei: Rough Endoplasmic reticulum
Red dots on Rough Endoplasmic reticulum: ribosome
Green line: microtubule (like highway)
Red lines around green line: actin (like roads up to the home)
alzheimer's disease: damaged on green line highway
Cancer: imbalance in microtubule and actin.
If highway grows continuously without removing old ones, it becomes the cancer.
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Object Rough Endoplasmic reticulum: Golgi complex which had been found by C. Golgi.
Partial area of Golgi complex enters into end of body:
There are also microtubule (green) and actin (red) around Golgi complex
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Let's zoom in Rough Endoplasmic reticulum
ribosome:
Small small unit, Large small unit
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Green line across ribosome: mRNA
Green curved dots: which pharmacy compnay want to know
because they can control the effect of drug if they know it.
Green dots embeds into membrane, and they becomes various ionic channel.
NR1: colored one
NR2: non-colored one
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Rough Endoplasmic reticulum which has ionic channel becomes separated into individual ones.
Separated Rough Endoplasmic reticulum forms trans golgi network (TGN)
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TGN can go to the end of body with delivering ionic channel into end of body
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Ionic channel is delivered through green line (highway, microtubule)
and red line (small roads, actin)
Kinesin: truck that delivers ionic channel.
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There is mLin complex on the truck Kinesin.
There are ionic channel on the mLin complex
Ionic channel is wrapped by separated Rough Endoplasmic reticulum
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Myosin: Small truck on the small road (red line)
Adapter on the myosin: Rab
There are ionic channel wrapped by Rough Endoplasmic reticulum on the Rab
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Let's zoom in "very end" where synapse is formed.
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postsynaptic membrane
It has phospholipid bilayer
exocyst (exo: exist=exodus, cyst: pocket, which means tool which is need when being existed), scafold, ionic channel, separated Rough Endoplasmic reticulum, snare complex
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Above complex object is embeded into phospholipid bilayer of postsynaptic membrane
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Embeded ionic channel moves into end of postsynaptic membrane
But note that ionic channel has tail
Overview:
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Under the tails, there are scafold:
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Under the scaffold, there are GKAP protein
GKAP: guanylate kinase associated protein
In molecular biology, P generally stands for protein or phosphorous
K generally stands for Kinase which attaches phosphorous to supply energy for molecular mechanism.
phosphatase: deattaches phosphorous
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One is the spar along with 2 GKAPs
Small protein next to spar is cript
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Colored one: NR1
Noncolored one: NR2
NR1 and NR2 are sub units which consist of NMDAR
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Since there are scaffold, AMPAR can stand on it.
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There are stargazin protein next to AMPA-R
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There are CAMK2 (Ca2+ calmodulin Kinase 2, 20 nanometer) next to tail of ionic channel
Path width of AMPAR, NMDAR is 10 nano meter
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calmodulin protein absorbs calcium, not make cells as like bone
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mGluR: protein, glutamate receptor
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Shank protein and Hemer are attached onto GKAP
Shank protein is composed of src homology and anklyn protein
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Homer has calciumn reservoir which has phospholipid bilayer
Door of calciumn reservoir is called IP_3 R (inositol triphosphate)
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If signal comes from center ionic channel,
that signal is passed and it opens IP_3 R
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mGluR has 2 Homers, and shank, cortactin protein, and red line (actin)
Calcium reservoir is linked by Rab and myosin
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There is SynGAP (Syn means synaptic) protein next to GKAP
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There is Fyn protein next to tail
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presynaptic membrane generally has pockets as well as small quantity of protein
postsynaptic membrane generally has large quantity of protein
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n methyl d aspartate receptor
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$$$Ca^{2+}$$$ enters through NMDAR
By trigger of $$$Ca^{2+}$$$, adenylyl cyclase activates
cyclase forms cyclic object
cyclase triggers cAMP
Protein kinase A is activated by cAMP
PKA inserts AMPAR
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$$$Ca^{2+}$$$ activates $$$PYK_2$$$ (protein tyrosin kinase 2)
$$$PYK_2$$$ activates Src (which is gene which promotes sarcoma) protein
Src activates NMDAR
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$$$Ca^{2+}$$$ activates $$$PKC$$$ (protein kinase C)
PKC activates $$$PYK_2$$$
PKC inhibits AMPAR
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$$$Ca^{2+}$$$ activates CaMK2
CaMK2 promotes generating AMPAR
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cAMP triggers RapGEF protein
RapGEF decomposes into Rap
And Rap is regularted by Spar
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$$$Ca^{2+}$$$ and PYK2 trigger RasGEF
RasGEF decomposes into Ras protein which is cancer protein and switch protein
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Ras activates PI3K which is enzyem which attach phosphorous
into 3rd location in benzen ring of phosphatidyl inositol
PI3K promotes generating AMPAR
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SynGAP regulates Ras
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Ras activates Raf
Raf activates MEK1,2
MEK1,2 activate ERK1,2
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ERK1,2 enter into nuclus
Activity triggers gene and DNA
DNA triggers RNA (transcription)
RNA performs translation into proteins
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Proteins are delivered via Rough Endoplasmic reticulum to insert ionic channel
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Morphology of spine changes (thinker)
It's memory
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When mGluR is attached by glutamate,
mGluR creates $$$G_{\alpha}$$$
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$$$G_{\alpha}$$$ triggers PLC (phosphorous lipaze C)
PLC opens $$$IP_{3}R$$$
$$$IP_{3}R$$$ releases $$$Ca^{2+}$$$
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$$$Ca^{2+}$$$ triggers PP2B
PP2B triggers PP1
PP1 regulates AMPAR
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NE: norepinephrine
E: epinephrine
DA: dophamine
SHT: serotonine
Ach: acetylcholine
NE, DA, SHT: metabolic
Channel
ionic: instant response
metabolic: slow mechanism
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glutamate: +, accelator
GABA: -, brake
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receptor for glutamate: AMPAR, NMDAR
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Ionic receptors
Glu: glutamate amino acid which is used as neurotransmitter
Glu receptor
AMPAR -> GluR1 - GluR4
NMDAR -> NR1 (NR1 has 8 variations)
(NR1-1a
NR1-2a
NR1-3a
NR1-4a
NR1-1b
NR1-2b
NR1-3b
NR1-4b)
NR2A - NR2D
(NR2C is abundant in the cerebellum)
(NR2D receptor shows at initial time of generation)
NR3A - NR3B
8+4+2=14
Kainate - Glu5 - Glu7, Ka1, Ka2
GABA has submodules as channels -> $$$\alpha, \beta, \gamma, \delta, \epsilon, \rho$$$
acetylcholine has channels -> $$$\alpha, \beta, \gamma, \delta$$$
nicotinic receptor has n in front of name so nAch
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Metabolic receptors
mGluR: metabolic receptors for glutamate
- mGluR1 - mGluR8
metabolic receptors for GABA
- GABA_A, GABA_B
metabolic receptors for dophamine
- D1 - D5
metabolic receptors for norepinephrine and epinephrine
$$$\alpha1, \alpha2, \beta1, \beta2, \beta3$$$
metabolic receptors for serotonine (5HT)
$$$5HT_1 - 5HT_7$$$
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Spine
Dendrite
GluR2, GluR3
GluR2 is attached by protein named AP2
Then, area becomes collapsed like this;
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This is called endocytosis
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GluR1 has long tail
Suppose there is GluR3 next to GluR1
They are uploaded onto membrane
CaMK2 and PI3K help them to be uploaded
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And they're inserted into membrane
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stargazin helps them to upload onto end of spine
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GluR2 and GluR3 are moved into center area
and it waits for "activity dependence"
If there is no activity dependence, it's deleted (degradation) by lysosome by using strong acid
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When density of NSF protein increases, it moves up
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Red intervals: region where alternative splicing occurs
Red dot: region where RNA editing happens
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alternative splicing
In RNA, there are active regions which create proteins
There are many possible combinations to create protein
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* Spine
* Red verticals: scaffold inside of spines
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* Cocaine is inserted
* Spines become thicker and larger
* LTP (Long Term Potentation): electrical pulses are kept
* Many mechanisms happen under the spines
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* alzheimer is LTD (Long Term Declaration)
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* scaffold is important because it's ground for mechanisms
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* Glutamate based sysnase
* GABA based synapse
* gephyrin: scaffold for GABA based synapse
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* Physiological (ordinary state)
* Acute cocaine (sudden addiction to cocaine)
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* NMDAR: NR1, NR2B
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NR2B has tail
At the end of tail, it has YEKL amino acid order
Y: tyrosin
E: Glutamate
K:
L: Lysin
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NR1 and NR2B moves to down
Space is cut by dyynamin protein
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There is protein called clathrin like a pincet
https://www.youtube.com/watch?v=-qMSF0pz1bA&list=PLWEQK2NI_UhL5cT7AcvGYknIEkazdTVQw
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Let's see the state of those who is addicted to Cocain, at spine level
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ORX1 receptor
Cocain molecule is attached to ORX1
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ORX1 triggers PLC
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NR1 (blue bar) small
NR2A (red bar) very much
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Many NR2A goes up to the membrane
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2B channel becomes many, which is the definition of the addiction
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View Alzheimer at spine level
Alzheimer is highly related to hippocampus
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nAch Receptor
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Ligand (red dot) as beta amyloid is attached to nAch-R
beta amyloid: Membrane insert protein
beta amyloid is cut, cut beta amyloid works as ligand
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$$$Ca^{2+}$$$ is in
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$$$Ca^{2+}$$$ triggers PP2B
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STEP protein is generated
STEP removes P from the protein, specifically, NR2B
This process is proceeded within 10 minutes
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You can see the red P
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P is removed by STEP
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AP2 is attached
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Channel moves
Number of 2B reduces
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2B is detached by clatin
lysosome degradation occurs
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View Schizophrenia at spine level
Schizophrenia is highly related to prefrontal cortex
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Receptor: ErbB4
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Ligand on the ErbB4: neuregulin
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PP2B is activated
STEP is activated
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NR2A has P
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NR2A reduces
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The ratio of NR2A and NR2B is important
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The ratio switches in 2 periods; development, hippocampus's LTP
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Activity dependent
Coincident detector
are well implemented in NMDA-R
The core concept in terms of NMDA-R is that
the ratio of NR2A/NR2B is important
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Invertebrates
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Vertebrates
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The life is the molecular system which performs "Darwin evolution"
which is in other words "activity dependent"
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Ribosome
mRNA
Raw polypeptide
Separated ribosome into large and sub units
Red square: final form of single protein
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P (which is label for energy) is attached to protein by kinase
P (which is label for energy) is detached from protein by phosphate
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