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