Lecture 9.

• Cell Communication.

  - Essential for infection, growth, and immune response.

  
• Cellular Processes are Coordinated and Regulated.

  
• How Does a Cell Know What to Do?

  - Transduce into response

  - Highly specific signals released

  - Single instruction to single destination

  - Signal is received

  - Signal converted into biochemical reactions

  - Cell carries out instruction.

  
• Intracellular Signalling.

  - Communication within the cell.
• Extracellular Signalling.

  - Communication outside the cell.
• Intercellular Signalling.

  - Communication between different cells.

  
• Spatial Regulation.

  - Processes occur in specific cellular compartments

  - Only cells that are needed respond.
• Temporal Regulation.

  - Processes occur when and as needed.
• Autocrine Signalling (auto = self, crine = separate).

  - Cell signals itself or identical cells.

  
• Juxtacrine Signalling (juxta = close).

  - Direct contact-dependent signalling between adjacent cells

  - Ligand embedded in membrane

  - Receptor on target cell membrane.

  
• Paracrine Signalling (para = beside).

  - Signals act on nearby, different cells

  - Ligand is short-lived

  - Received and degraded quickly

  - Prevent further action.

  
• Endocrine Signalling (endocrine = in blood).

  - Signals travel long distances via bloodstream

  - Distant target.

  
• Synaptic Signalling (junction, gap).

  - Neurotransmitter release at synapses

  - Ligand transported along axon.

  
• Extracellular Signals.

  - Include hormones, ions, and chemical signals

  - pH

  - Osmotic strength

  - Oxygen

  - Light

  - Population density.
• Signal Types.

  - Include amino acids, proteins, and gases.
• E.g. calcium-mediated rapid movements in Mimosa pudica.

  - Plant is touched, calcium fluoresces = leaf folds up

  - Calcium points going down vein = each leaf contracts

  - Molecule binding to calcium = as calcium is released

  - Message/signal passed down vein of plant = leaves start to close.
• Cell Signalling Stages.

  - Reception, transduction, and response

  - Transduction pathway complicated = small reaction that triggers lots of things.

  
• What is the mechanism by which an extracellular is released from the producer cell?

  - Exocytosis.
• How does it work?

  - Binds to receptor

  - Highly specific

  - Exocytosis > diffusion > sits on cell surface > cleaved protein

  - Cleaved protein can act as a ligand = bc once that protein is cleaved it releases something.

  
• Ligand/signal.

  - Molecule that binds to a receptor.
• Reception.

  - Many different types of receptors.

  
• Ion Channel Receptors.

  - Transport ions like Na+ and Ca2+

  - Narrow, highly selective

  - Passive transport

  - Involved in synaptic signalling

  - Intracellular mediator.

  
• E.g. K+ channels.

  - 3 states: resting, activated and inactivated

  - Closed in resting state, opened after stimuli activation

  - All have a central pore TM helices and regulatory domain.

  
• G-Protein Coupled Receptors.

  - Involve GTP binding and signal transduction

  - Target proteins are enzymes or ion channels.

  
• What type of protein is the receptor?

  - Transmembrane.
• What type of protein is the G-protein?

  - Lipoprotein.
• What type of protein is the enzyme?

  - Transmembrane.
• How does it work?

  - 1. Signal binding causes conformational change

  - 2. Receptor binds to G-protein

  - 3. GDP converted to GTP

  - 4. GTP bound protein interacts with enzyme triggering activation

  - 5. GTP slowly hydrolysed back to GDP.

  
• Amphipathic Helix.

  - Alpha helix with hydrophobic and hydrophilic regions

  - Found in membrane proteins

  - Help anchor protein to lipid bilayer.
• Enzyme Coupled Receptors.

  - Two types

  - Associate with enzymes causing activation.

  
• Tyrosine Kinases.

  - Enzyme coupled receptors that phosphorylate tyrosine residues

  - Auto-phosphorylation

  - Kinases phosphorylate.

  
• Transduction - Extracellular Molecule Triggers Intracellular Cascade.

  - Multiple steps = specific.

  
• Small Signal goes a Long Way.

  - Single ligand can be detected at low concentrations (10⁸)

  - Ligand/signal can be amplified = through phosphorylation

  - Ligand can be amplified massively = one change will impact multiple proteins.

  
• Phosphorylation.

  - Addition of phosphate group, altering protein function.

  
• Kinases.

  - Enzymes that add phosphate groups to proteins

  - When kinase binds there is a change in binding partners and structure.
• How does it work?

  - Phosphorylation happens at alcohol group (OH group)

  - Phosphorylated amino acid defines the type of kinase.

  
• Phosphatases.

  - Enzymes that remove phosphate groups from proteins

  - When phosphatase binds there is a change in activity, interaction, protein stability and subcellular localisation.
• Multiple phosphorylation sites.

  - Trigger many different pathways

  - Message can be sent in wrong direction

  - Complex interactions and network.

  
• Is it quicker to alter protein function or is it quicker to alter protein synthesis? Is synthesis quicker than function?

  - Protein function is quicker

  - Altering protein synthesis requires to go through the whole process

  - Can alter protein function quickly by phosphorylation, or by ubiquitination

  - Altering protein function is quicker and easier compared to making a different protein altogether.

  
• Nuclear Response.

  - Cellular response involving gene expression changes.