Lecture 9: Cell Communication Bio 93: DNA to Organisms Lecture 9: Cell Communication What happens when you get scared?

Lecture 9: Learning Objectives 9.1 – Explain how cell signaling pathways proceed via the steps of reception, transduction, and response 9.2 – Explain the steps of the epinephrine-GPCR pathway 9.3 – Predict what might happen to cellular pathways if they are interrupted

Lecture 9: Key terms Gap junction Protein phosphatase Paracrine signaling Phosphorylation Synaptic signaling Dephosphorylation Endocrine signaling Second messenger Hormones Cyclic AMP (cAMP) Reception Adenylyl cyclase Transduction Epinephrine Response Glycogenolysis Signal transduction pathway Protein kinase A Ligand Phosphorylase kinase G protein-coupled receptor (GPCR) Glycogen phosphorylase Intracellular receptor Protein kinase

What happens when you get scared? 9.1 Epinephrine What type of signaling pathway is this? How does epinephrine get to the muscles of the body?

Epinephrine induces glycogenolysis In muscle cells How does this happen? Epinephrine Glucose 9.2

1 2 Explain what is going on in this figure to your neighbor EXTRACELLULAR FLUID CYTOPLASM Plasma membrane 1 Reception 2 Transduction 3 Response Receptor Glycogen- olysis 1 2 3 Relay molecules Epinephrine How is a signaling pathway with testosterone different? 9.1 Can you draw the detailed pathway for how epinephrine induces glycogenolysis? 2 9.2

Cytoplasm of a muscle cell Extracellular fluid Cytoplasm of a muscle cell

Glycogen phosphorylase Adenylyl cyclase GPCR Glycogen phosphorylase GTP cAMP Epinephrine Glucose ATP GDP Protein kinase A G protein Phosphorylase kinase Glycogen

2 What is the correct order of proteins that the signal passes through? (not all proteins are listed) A – glycogen phosphorylase B – adenylyl cyclase C – GPCR D – Protein kinase A E – cAMP 9.2

G protein coupled receptor (GPCR) structure GPCRs structure: Receptor is a multipass protein, crossing membrane 7 times with specific orientation to form cylindrical structure with deep ligand binding site at center GPCRs interact with G proteins associated with the cytosolic leaflet of the membrane http://www.nature.com/scitable/topicpage/gpcr-14047471

What do kinases do? By adding a phopsphate group to a protein, the kinase induces a conformational change in the protein, resulting in a change in the proteins function. Bio 93 (Summer 2017), Copyright © 2017, Dr. Salme Taagepera. All rights reserved.

2 What would NOT happen if protein kinase A was blocked by a drug? A – cAMP would be produced from ATP B – Intracellular [glucose] would increase C – Epinephrine would bind to the GPCR D – The G protein would diffuse in the membrane Figure 11.6 on page 224 2 9.2 9.3

Question: How does epinephrine affect skeletal muscle metabolism? Hypothesis: Epinephrine increases glycogenolysis Experiment: Injected epinephrine or saline (control) into rat hindlimb musculature, measured many parameters over time Measured: Phosphorylase kinase activity Protein kinase A activity Cellular glucose concentration Glycogen synthase activity 9.2

9.2 What will happen to these parameters for control (saline) and epinephrine injections? 3 Protein kinase A activity [Glucose] Time (minutes of infusion) Time (minutes of infusion) Phosphorylase kinase activity Time (minutes of infusion) glucose

9.2 What will happen to these parameters for control (saline) and epinephrine injections? 3 Glycogen synthase activity Time (minutes of infusion) glucose

What results do you think they observed for glycogen synthase activity? Red – saline Blue – epinephrine B 3 9.2

Other effects of adrenaline… Allergic reactions can cause body to go into anaphylactic shock: decreased heart rate dilated blood vessels closed airways Epinephrine: increases heart rate constricts blood vessels opens the airways https://www.slideshare.net/j3di79/chapter-15-hormones-lesson-2-effects-of-adrenaline-and-table-of-comparison-btw-nervous-and-hormonal This is why Epi pens work! Bio 93 (Summer 2017), Copyright © 2017, Dr. Salme Taagepera. All rights reserved.