Cell Communication

2 Major Mechanisms of Communication Negative Feedback: Stopping a signal in response to a sufficient amount of the end product; “counter-acting” Ex: Regulating Blood Sugar Positive Feedback: Cell signal will continue as long as stimulus is available; “promoting” Ex: Oxytocin (hormone that stimulates muscle contraction)

Cell Signaling Animal cells communicate by: Direct contact Gap junctions Antibodies Local Signaling Paracrine: vesicle-mediated Growth Factors Synaptic: channel-mediated Neurotransmitters Long distance (hormones)

3 Stages of Cell Communication: Reception: Ligand binds to receptor protein on cell’s surface, causing protein to change shape Transduction: Convert signal to a form that can bring about a cellular response; usually multi-step Response: Cellular response to the signal molecule; may cause cell to produce something or regulate a cellular processes

Reception

Transduction

Response

1. Reception Binding between signal molecule (ligand) + receptor is highly specific. Types of Receptors: Plasma membrane receptor proteins water-soluble ligands Intracellular receptor proteins (cytoplasm, nucleus) hydrophobic or small ligands Most often are steroids Ligand binds to receptor protein  protein changes SHAPE  initiates transduction signal

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Ligand binds to GPCR, changing shape of GPCR Shape change causes G protein subunit to be released Released G protein subunit then docks with another protein (or enzyme), which will relay the signal further

G-Protein-Coupled Receptor https://www.youtube.com/watch?v=qOVkedxDqQo

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Ligand binds and kinases dimerize Activated kinases accept phosphate group from ATP (activates kinase) Relay proteins take phosphate groups away to activate multiple cellular response

Receptor Tyrosine Kinase https://www.youtube.com/watch?v=kiHAdan2AOY

Plasma Membrane Receptors G-Protein Coupled Receptor (GPCR) Tyrosine Kinase Ligand-Gated Ion Channels Ligand binds to protein receptor, allowing gate to open Ions are able to pass through cell membrane When ligand detaches, gate closes

Ligand-Gated Ion Channel https://www.youtube.com/watch?v=Du-BwT0Ul2M

2. Transduction: multi-step signal that relays chemical signal from receptor to response Two methods of transduction: Phosphorylation Cascade Involves transfer of phosphate groups to/from ATP within protein pathway Kinases: activate proteins (add phosphate) Phosphatases: deactivate proteins (remove phosphates) Second messengers Use of non-protein molecules to relay signals; sometimes activate cascades

Results in phosphorylation (activation) of thousands of proteins Energy is taken from original relay molecule to activate cascade, which then takes the “activation” signal to a specific protein (the target of the original signal), to elicit a cellular response

Second Messengers small, nonprotein molecules/ions that can relay signal inside cell Eg. cyclic AMP (cAMP), calcium ions (Ca2+)

cAMP cAMP = cyclic adenosine monophosphate GPCR  activates/releases G proteintravels to adenylyl cyclase (convert ATP to cAMP)  activate protein kinase A

3. Response Regulate protein synthesis by turning on/off genes in nucleus (gene expression) Regulate activity of proteins in cytoplasm

Let’s visualize this! Epinephrine pathway: https://www.youtube.com/watch?v=qOVkedxDqQo

Signal Transduction Pathway Problems/Defects: Examples: Diabetes Autoimmune disease Cancer Drugs (anesthetics, antihistamines, blood pressure meds)

Viagra Used as treatment for erectile dysfunction Prolongs signal to relax smooth muscle in artery walls; increase blood flow to penis

Apoptosis = cell suicide Cell is dismantled and digested Triggered by signals that activate cascade of “suicide” proteins (caspase) Why? Protect neighboring cells from damage Animal development & maintenance May be involved in some diseases (Parkinson’s, Alzheimer’s)

Apoptosis of a human white blood cell Figure 11.19 Apoptosis of human white blood cells Left: Normal WBC Right: WBC undergoing apoptosis – shrinking and forming lobes (“blebs”)

Effect of apoptosis during paw development in the mouse Figure 11.21 Effect of apoptosis during paw development in the mouse