PSYC 211 Study Guide - Final Guide: Serum Response Factor, Mitosis, Analgesic

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11 Aug 2016
Department
Course
BIOL 201 – Cell Biology and Metabolism C. Aikins
Notes III: Topic 16 - 17 (Nervous system) Winter 2011
1
Topic 16 – Hormones and Intracellular Communication
Overview
Chemical classes
Made of peptides (proteins), proteins, modified amino acids, water soluble
lipid soluble hormones (steroids)
There are different styles of intercellular signalling
Endocrine signalling
hormone is secreted into the blood by an endocrine gland, affecting distant target cells
Hormones: Ex. Epinephrine, Thyroxin, adrenaline
Secreted in small amounts
Paracrine signalling
secretory cells secretes aqueous, hydrophilic molecules into the ECF and bind to receptors on the surface of an
adjacent target cell
One cell to an immediately adjacent cell eg neurotransmitters
Receptor-ligand binding produces the effect, as aqueous molecules can get through the lipid membrane directly
Synapses in the nervous system function via this mechanism
Autocrine signalling
secretory cells stimulate themselves by releasing the signal into the ECF and having them interact with their
own receptors
Cancers
Typical in the immune system for amplification (positive feedback mechanism)
Causes increased number and increased proliferation of cells
Have regulatory molecules to prevent a build-up
Contact Mediated (Signalling by Plasma Membrane-attached proteins)
signalling cell interacts directly with the adjacent target cell via (embryonic nerve fibre guidance)
embryonic nerve fibre guidance
Ligand is either an integral membrane protein or an extracellular matrix protein (protein outside of the cell)
Adjacent cell has a receptor for it
Cells can communicate via direct contact or by signalling
Ex. Nerve growth factor (NGF)
Intercellular Signal Receptor Systems in Cells – Synaptic Transmission
Signal transmitted by ligands binds to receptors, which in turn produce internal signals that transduce the extracellular signal
into a cell-specific signal
Lipid soluble
Lipid-soluble hormones can dissolve through the plasma membrane
Do not have membrane-surface receptors, don’t need them
Have to be bound to proteins that give them a water soluble shell so they can move in the blood stream
Don’t get broken down quickly
Bind to intracellular receptors
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Receptors are transcription factors that have ligand recognition sites
They bind to the TFs in the cytoplasm, diffuse into the nucleus and increase/decrease transcription
Aka become activated by ligand
Response is slightly delayed as it takes time for transcription to begin
Also produces a constant effect, as the hormone hangs out in the nucleus for a while
Overall, long-lasting, slow effects
For water soluble have different receptors:
G-protein coupled receptor (GPCR)
Hetero-trimeric G protein
Bind ligands at the cell surface
Protein has 7 transmembrane segments
G-protein is the 3 subunits that has cytoplasmic segments
Not an enzyme, just an activator of other molecules in the sequence
Receptor protein kinases (RPK)
Binds ligand, enzyme becomes active as a protein kinase
Cytoplasmic end is activated when the ligand is bound
Activity is to phosphorylate
Tyrosine kinases
Will only phosphorylate the amino acid tyrosine
Ion Channels
Ligand gated ion channels
Open when bound to ions
Most important point is that via the change in molecular conformation of the receptor after ligand-binding, the signal is
carried across the membrane
Specialty of living organisms to bring signals from the outside to the inside
After being carried across the membrane, there can be rapid effects or slow effects
Modification of cellular metabolism, function, or movement
Tend to be more rapid
Modification of gene expression or development
These take longer
Receptors can produce changes that will shut itself off
Part of the regulation of the receptor comes from the activated receptor itself
Ligand dissociation attenuates the signal
Lipid Soluble Hormones – Steroids & Others
Effects
Develop over time and last for a long time
Slow and long lasting
Effective in extremely low doses: they must have very high affinity receptors
Usually present in body in very low amounts, which is why taking steroids are dangerous
All of the steroid hormones come from cholesterol
Estradiol (estrogen), Testosterone
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Cortisol stress hormones that acts as an immunosuppressant, increases blood sugar and increases blood pressure
Vitamin D (produced by the effect of sun on cholesterol)
Anti-inflammatory
Receptor Proteins for Lipophilic Molecules
Receptors proteins for steroid hormones has similar structures
“Ligand activated transcription factors”
No conservation in variable region, but very highly conserved DNA-binding. Ligand-binding has a decent amount
of homology, in part because the steroids have similar structures
Ligand-binding domain binds the specific ligands
At the C-terminus
15-57% amino acid identity
DNA-binding domain region that binds the DNA when initiating transcription
In the centre of the molecule
68aa
42-94% amino acid identity most highly conserved!!
Variable region activation domain at the N-terminus
Involved in binding other TFs to mediate the transcription or inhibition of transcription
Responsible for binding cofactors that will mediate the different responses from the different ligands
100-500aa
0% amino acid identity no conservation!!
Mechanism of steroid hormone activity
Aka cytoplasmic receptor activity
Some classes of receptors are present in the cytoplasm and have inhibitor molecules
In the resting state its inactivated by inhibitor molecules that bind to LBD
Inhibitor blocks a nuclear localization signal on the cytoplasmic receptor
When the hormone binds, the inhibitor dissociates
With the NLS exposed, moves into the nucleus and homodimerizes
Homodimer binds to a response element in the DNA
Receptors of the dimer are facing each other
Means that the response element has a DNA sequence that is present twice, but facing opposite
directions antiparallel
In this case, would bind to other TFs and initiate transcription of the gene with this response element
Can tag the LBD with a fluorescent tag to view it
Can watch it getting localized to the nucleus
Hormone Response Elements
DNA sequences that are bound by the lipid-soluble hormone receptors
Naturally can fall into two categories:
Homodimers: Antiparallel (Inverted repeats)
Cytoplasmic receptors that translocate to the nucleus
Ex. Estrogen receptor elements, Glucocorticoid REs
Cytoplasmic, bind ligand, homodimerize
Heterodimers: Direct repeats
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