CELL COMMUNICATION Cell Communication Conserved Shape specific signal in Evolution molecules and receptors
Ex mating of yeast Signal Transduction Pathway series of steps that changes the cell Found in prokaryotes, eukaryotes, yeast,
bacteria Quorum Sensing in bacteriaBiofilms Long distance signaling in multicellular organisms Stages of Cellular Signaling
Earl Sutherland studied how adrenaline (norepinephrine) breaks down glycogen for respiration (Fight or Flight) Step 1: Reception: a chemical signal must be detected by a receptor protein molecule Step 2: Transduction: The signal molecule changes the receptor protein causing a specific cellular response- Signal Transduction Pathway
Step 3: Response: The cell responds in a specific way to maintain homeostasis https://www.google.com/url?sa=i&source=images&cd=&ved=0ahUKEwj48uehlJreAhXQm-AKHao8AH8QMwg8KAAwAA&url=https%3A%2F%2Fwww.nobelprize.org%2Fprizes%2Fmedicine%2F1971%2Fsutherland %2Ffacts%2F&psig=AOvVaw13p34gBfW8EIn89mYGehRl&ust=1540301472087846&ictx=3&uact=3 https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwj38YyulpreAhWudN8KHROcCNIQjRx6BAgBEAU&url=http%3A%2F %2Fvaydile.euforic.co%2Fg-protein-coupled-receptors%2F&psig=AOvVaw24O_2FK36J0WxrDNxJCN2a&ust=1540302025048495
G Protein Receptors (GPCR) G Protein Couple Receptor Similar in structure within eukaryotes A single polypeptide with 7 transmembrane alpha helices Loops in protein form binding sites (outside the cell) and G protein on the inside Diverse in function
Embryonic development, smell, taste Many diseases are a result off malfunctions of G proteins Cholera Pertussis botulism https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwilg8nflZreAhUSmeAKHQnWBXoQjRx6BAgBEAU&url=https%3A%2F%2Fbio.libretexts.org%2FTextMaps %2FBiochemistry%2FBook%253A_Biochemistry_Free_and_Easy_(Ahern_and_Rajagopal)%2F08%253A_Signaling%2F8.4%253A_G-
GPCR 1. GDP (Guanine Di or Tri Phosphate- similar to ADP/ATP) binds to G protein (inactive) 2. A signal molecules binds to the receptor, the G protein with the help of an enzyme, changes shape, causing GTP to replaces GDP and activating the protein 3. G protein now leaves the receptor, binds to the enzyme and triggers
the next cellular response (similar to ligands) Shape changes are temporary as the G protein is also GTPase which hydrolyzes GTP to GDP + Pi https://upload.wikimedia.org/wikipedia/commons/thumb/8/8e/G_protein.jpg/550px-G_protein.jpg Receptor Tyrosine Kinase Plasma membrane enzymatic protein
Transfers phosphate groups Transfers a phosphate group from ATP to tyrosine on a substrate protein RTKs are used to activate multiple pathways Cell growth and reproduction Different from GPCRs (only one pathway)
http://bio1151b.nicerweb.net/Locked/src/Locked/media/ch11/11_07bTyrosineKinases.jpg RTK 1. Receptors are monomers, each with its own ligand-binding site 2. Signaling molecule binds to two receptor monomers, forming a dimer 3. Dimerization activates the RTK region of the monomer and adds a phosphate from ATP to the tail of a tyrosine 4. Now that it is active, relay proteins inside the cell can recognize the receptor and a signal transduction pathway ensues
https://www.google.com/url?sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwiq4tKh76LeAhWCTt8KHX6sAvAQjRx6BAgBEAU&url=https%3A%2F%2Fwww.creative-biostructure.com%2Fcustom-mempro %25E2%2584%25A2-pentameric-ligand-gated-ion-channels-services-45.htm&psig=AOvVaw1Q4Da_Oj2w-X2zN2w0QWWN&ust=1540600757935323 Ion Channel Receptors A signaling molecule binds as a ligand which changes the shape of the receptor protein and
the gate opens or closes A ligand binds to a specific site on the transmembrane protein The gate opens and the channel opens for ions to flow through When the ligand leaves, the receptor closes Neurotransmitters Transfer across the synapse of two neurons
Bind to the receiving cell An electrical signal flows through the neurons (affecting ioin gated channels) Intracellular Receptors Found in cytoplasm or nucleus of cells Successfully passed through the membrane by being small and/or hydrophobic (ex: steroid and thyroid hormones
Binds with hormone-receptor complex and changes the shape causing a response turning on genes DNA mRNA Ribosome Protein Proteins called transcription factors control which genes are turned on Transduction pathway ensues http://cnx.org/resources/f45222d95593c5d576b75d69d74eaec0/1803_Binding_of_LipidSoluble_Hormones.jpg
Transduction Pathways Multi-steps pathways signaling steps one to the next https://pharmaceuticalintelligence.files.wordpress.com/2014/08/ signaltransduction_simple.jpg Phosphorylation and Dephosphorylation
Adding or removing phosphate groups through a series of steps Protein phosphates enzymes that rapidly remove Cyclic AMP or cAMP Cyclic adenosine
monophosphate Made from ATP by adenylyl cyclase Assists in G protein signaling pathways An example of signal transduction cascade involving cyclic AMP
The binding of adrenaline to an adrenergic receptor initiates a cascade of reactions inside the cell. The signal transduction cascade begins when adenylyl cyclase, a membrane- bound enzyme, becomes activated by Gprotein molecules associated with the adrenergic receptor. Adenylyl cyclase creates multiple cyclic AMP molecules,
which fan out and activate protein kinases (PKA, in this example). Protein kinases can enter the nucleus and affect transcription. 2010 Nature Education All rights reserved. Cholera
Bacteria form a biofilm producing a toxin on the small intestine The toxin is an enzyme that modifies a G protein responsible for salt and water secretion GTP does not become GDP, resulting in high concentrations of cAMP, causing a disruption in salt and water homeostasis and dehydration https://www.rdmag.com/article/2017/05/cdc-recommends-cholera-vaccine-us-travelers Importance of Calcium
Ca2+ used as a messenger Muscle cell contraction Cell division Plant cell greening Secondary messenger in GPCR and RTK Concentration higher in extra cellular fluid cytoplasm therefore they are actively transported into the ER Moves into the mitochondria through chemiosmosis when levels in cytosol are
high Secondary messengers IP3- inositol triphosphate
DAG0 diacylglycerol http://www.sivabio.50webs.com/ip13.jpg Cellular Response Reactions occur when specific genes/proteins are turned on or off Synthesis through gene expression Occurs in nucleus or cytoplasm
Signaling pathway tend to increase the cellular response Specific points along pathway provide regulation/control Scaffolding proteins enhances the productivity of the pathway or can act as a relay protein Pathways can branch out- ex: Wiskott-Aldrich syndrome https://upload.wikimedia.org/wikipedia/commons/6/6e/Metabolic_Metro_Map.svg
Cellular Pathway Endings Apoptosis: programmed cell death Organelles break up DNA to protect neighboring cells from damage Most pathways signaled by outside ligand from a neighboring cell Ligand binds and activates the caspases that carry out apoptosis Caspases are proteins that control cell deaths 15 different types of caspases in mammals
Cytochrome C from the ETC in the mitochondria acts as a caspase Cell death can come from internal signals DNA with irreplaceable damage Rough ER with mutated protein folding Similarities between organisms show early development in
eukaryotes Failure of apoptosis in mammals could result in webbing of digits https://images.wisegeek.com/small/diagram-of-apoptosis.jpg https://www.google.com/url? sa=i&source=images&cd=&cad=rja&uact=8&ved=2ahUKEwig97W8qqfeAhUMmeAKHa1pDwoQjRx6BAgBEAU&url=h
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