signal transmission & gene expression
DESCRIPTION
AKA – Cell Signaling Basics (we will revisit this topic during body systems). Signal Transmission & Gene Expression. Signal Transduction Pathway . “Signal” = chemical message that moves throughout body 2 types of signal transmissions Intercellular – move from cell to cell to cell - PowerPoint PPT PresentationTRANSCRIPT
Signal Transmission & Gene Expression
AKA – Cell Signaling Basics (we will revisit this topic during body systems)
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)
• 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
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
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
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
• 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
• 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
Why bother with all these steps?
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
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
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
Ex: Botulinum Toxin (BTX)• Caused by bacterium
Clostridium botulinum• Toxin inhibits
acetylcholine nt (signal) from being released thus inhibiting muscle contraction• Leads to paralysis