signal transmission & gene expression aka – cell signaling basics (we will revisit this topic...
TRANSCRIPT
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Signal Transmission & Gene Expression
AKA – Cell Signaling Basics (we will revisit this topic during body systems)
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Signal Transduction Pathway • “Signal” = chemical message
that moves throughout body
• 2 types of signal transmissions
– Intercellular – move from cell to cell to cell• Ex: Hormones of endocrine
system, neurotransmitters of nervous system
– Intracellular – move within cell itself• Ex: Apoptotic pathway
(mitochondrial mediated)
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• Chemical messages (“signals”) can affect cell in two ways:
1. Immediate effect on cell function (change what cell is doing)
2. Lead to gene expression via DNA transcription and protein translation
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1. Immediate Affect
• A message (chemical signal) is transduced (and usually amplified) into actions within cell
• Usually initiates a phosphorylation cascade which passes an energy-rich phosphate from one protein to another to another until desired action is carried out
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Generic Pathway
• Reception – Chemical message (ligand) docks at receptor on cell membrane and changes its shape
• Transduction – switching message from chemical signal received on cell outside to chemical messages on interior of cell
• Response – Signal transduction cascade occurs until end result is reached
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Ex: Epinephrine Signaling• Epinephrine (ligand) is released by adrenal
gland during “fight or flight” response
– Ligand is a chemical that can't get through cell membrane thus binds receptor on outside
• Epinephrine travels through body and binds to receptors on the outside of liver cells (high storage of glycogen)
• Epinephrine receptor is a G-protein coupled receptor
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• G-protein is embedded within cell membrane; has three subunits inside the cell
• Ligand binding changes the conformation of the GPCR and causes it to release alpha subunit
• Alpha subunit moves to another protein called adenylyl cyclase
• Binding causes conformational change which activates protein (enzyme)
• Enzyme converts ATP → cAMP
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• cAMP – (secondary messenger) targets a protein kinase that has 4 subunits
• 2 catalytic (speed up rxn rate)
• 2 regulatory (regulate catalytic subunits)
– If reg. subunits are attached to cat. → no action
– cAMP binds to regulatory subunits allosteric change in protein catalytic subunits are released
• Catalytic subunits get phosphorylated (activated)
• Active catalytic subunits act on enzymes w/in cell
• In this example, they activate phosphorylase, which breaks apart glycogen to release glucose
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Why bother with all these steps?
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2. Change Gene Expression• Pathway is the same UNTIL the catalytic
subunits are activated
• There are no proteins for these to act on, so instead they activate CREB (a transcription factor)
• CREB binds to DNA upstream of gene to be expressed, bends DNA to facilitate transcription of mRNA, mRNA is translated into a protein called phosphatase which is able to break down glycogen
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Changes to Pathways
• “Correct” signal transduction pathways are under strong selective pressure
• Changes that result in ineffective pathways are generally bad.
• 2 examples:
• Diabetes
• Botulism toxin
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Ex: Diabetes Type I
• Mutation results in autoimmune destruction of pancreatic beta cells (insulin producing cells)
• Inability to produce insulin affects ability of glucose to enter cells
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Ex: Botulinum Toxin (BTX)• Caused by bacterium
Clostridium botulinum
• Toxin inhibits acetylcholine nt (signal) from being released thus inhibiting muscle contraction
• Leads to paralysis