Chapter 4 - Membranes and Signalling PDF

Chapter 4 Membranes and Signalling  An Overview of the Structure of Membranes a. The fluid mosaic model of membranes b. Experimental evidence in support of the fluid mosaic model Fluid Mosaic Model of Membranes Consist of a fluid lipid bilayer in which proteins are embedded and f...

Chapter 4 Membranes and Signalling  An Overview of the Structure of Membranes a. The fluid mosaic model of membranes b. Experimental evidence in support of the fluid mosaic model Fluid Mosaic Model of Membranes Consist of a fluid lipid bilayer in which proteins are embedded and float freely  Membranes are NOT ____ Function: 1. Protection 2. Allow selective exchange of molecules between cell and environment Fluid Mosaic Model Extracellular Matrix Membrane Asymmetry Membranes are asymmetrical Membrane proteins of one half of the bilayer are structurally and functionally distinct from the other half Fluid Mosaic Model is Supported by Experimental Evidence: Membranes are Fluid Therefore movement of proteins Fluid Mosaic Model is Supported by Experimental Evidence: Membrane Asymmetry Different number, shape and size particles The Lipid Fabric of a Membrane a. Phospholipids are the dominant lipids in membranes b. Membrane fluidity c. Organisms can adjust fatty acid composition  Phospholipid Bilayers Non Maintaining Proper Fluidity Fluidity of lipid bilayer dependent on how densely individual lipid molecules can pack together Influenced by two major factors: 1. Composition of lipid molecules 2. Temperature 1. Composition  Less dense, more fluid 2. Temperature If temperature drops low enough, phospholipid molecules become closely packed, and membrane forms highly viscous semisolid gel Fluidity of membrane related to degree to which membrane lipids are unsaturated Most membrane systems have mixed population of saturated and unsaturated fatty acids Adjusting Fatty Acid Composition Proper fluidity is maintained by adjustment of fatty acid composition Desaturases: Enzymes that produce unsaturated fatty acids during fatty acid synthesis Regulation of desaturases --> membrane fluidity Desaturases Increase temp  decrease ________  Sterols At high temperatures Decreases fluidity At low temperatures  Increases fluidity Membrane ______ 5.3 Membrane Proteins a. The key functions of membrane proteins b. Integral membrane proteins c. Peripheral membrane proteins  Four Key Functions of Membrane Proteins Transport Enzymatic Signal transduction Attachment/recognition Two Structural Categories of Membrane Proteins 1. Integral membrane proteins 2. Peripheral membrane proteins 1. Integral Membrane Proteins Proteins embedded in phospholipid bilayer Composed of predominantly nonpolar amino acids usually coiled into alpha helices Transmembrane proteins: Most integral proteins Membrane Protein Structure Transmembrane Proteins 2. Peripheral Membrane Proteins On surface of membrane Do not interact with hydrophobic core Held together by noncovalent bonds Most on cytoplasmic side of membrane Made up of mixture of polar and nonpolar amino acids 5.4 Passive Membrane Transport a. Passive transport is based on diffusion b. The two types of passive transport: Simple and facilitated c. Two groups of transport proteins carry out facilitated diffusion d. Osmosis: The passive diffusion of water Passive Membrane Transport Hydrophobic nature of membrane restricts free movement of many molecules Passive transport: Movement of a substance across a membrane ______ need to expend chemical energy (ex. ATP) Passive Transport and Diffusion Passive transport driven by diffusion Diffusion: Net movement of substance from region of higher to lower concentration Rate of diffusion depends on the concentration difference or concentration gradient Two types: 1. Simple Diffusion 2. Facilitated Diffusion  Simple Diffusion Unstable Stable 1. Simple Diffusion Simple diffusion: Passive transport of substances across lipid portion of membranes with concentration gradients Small uncharged molecules move rapidly Large or charged molecules may be strongly impeded from crossing membranes 2 Factors that influence Diffusion: Size and Charge of Molecules 2. Facilitated Diffusion Facilitated Diffusion: Passive transport of substances at rates higher than predicted from their lipid solubility – Depends on membrane proteins – Follows concentration gradients – Is specific for certain substances – Becomes saturated at high concentrations of transported substance Transport Mechanisms Transport Proteins Carry Out Facilitated Diffusion: Integral membrane proteins 1. Channel proteins - Water and ions (ex. K+ and Na+) 2. Carrier proteins - Specific single solutes (ex. sugars and a.a.) Channel Proteins Diffusion Diffusion Gated channel  Carrier Proteins Diffusion Conformational Change Simple versus Facilitated Diffusion Saturation  Osmosis: The Passive Diffusion of Water Osmosis: Net diffusion of water molecules – Across a selectively permeable membrane – In response to differences in concentration of solute molecules Selectively permeable membrane must allow water molecules to pass but not solute molecules Simple or facilitated Tonicity Water moves: – from hypotonic solution (lower concentrations of solute molecules) to hypertonic solution (higher concentrations of solute molecules) When solutions on each side are isotonic: – No NET osmotic movement of water in either direction Tonicity and Osmotic Water Movement 5.5 Active Membrane Transport a. Active transport requires energy b. Primary active transport moves positively charged ions c. Secondary active transport moves both ions and organic molecules Active Membrane Transport Active transport requires a direct or indirect input of ________ derived from ATP hydrolysis Moves substances against their concentration gradients; requires cells to expend energy Depends on membrane transport proteins Specific for certain substances Can be saturated Two Kinds of Active Transport 1. Primary active transport: Same protein that transport substance also hydrolyzes ATP to power transport directly 2. Secondary active transport: Transport indirectly driven by ATP hydrolysis – Transport proteins do NOT break down ATP – Instead use a favourable concentration gradient of ions as the energy source 1. Primary Active Transport Moves positively charged ions across membranes – H+ pumps (proton pumps) – Ca2+ pump – Na+/K+ pump Primary Active Transport  Na+/K+ Pump But 3 Na+ went out and only 2 K+ came in?? Ion Pumps Maintain Membrane Potential Membrane potential is the voltage difference across a membrane -50 to -200 mV Electrochemical gradient – concentration difference and an electrical charge difference  2. Secondary Active Transport a. Symport - Cotransported solute moves through membrane channel in same direction as driving ion b. Antiport – Driving ion moves through membrane channel in one direction, providing energy for active transport of another molecule in opposite direction Secondary Active Transport Transport Mechanisms Lap-Chee Tsui (Toronto Hospital for Sick Kids) Discovered defective gene that causes cystic fibrosis Codes for cystic fibrosis transregulator protein (CFTR)  Channel protein that allows chloride ions to pass across plasma membrane Three nucleotide deletion  loss of phenylalanine Improper folding and structure  improper function 5.6 Exocytosis and Endocytosis a. Exocytosis releases molecules to the outside by means of secretory vesicles b. Endocytosis brings materials into cells in endocytic vesicles Transporting Larger Substances Exocytosis and endocytosis – Move large molecules, particles in and out of cells Both require energy  Exocytosis Secretory vesicle carries secreted materials – Moves through cytoplasm and contact plasma membrane – Vesicle membrane fuses with plasma membrane, releasing contents to cell exterior – Replenish plasma membrane  Exocytosis Secretory Cytosol Outside vesicle cell Protein inside vesicle Protein in vesicle Plasma membrane membrane 1. Secretory vesicle approaches 2. Vesicle fuses with 3. Proteins inside vesicle plasma membrane. plasma membrane. are released to the cell exterior; proteins in vesicles membrane become part of plasma membrane.  Endocytosis Encloses materials outside cell in plasma membrane – Pockets inward and forms endocytic vesicle on cytoplasmic side Two main forms 1. Bulk-phase (pinocytosis) 2. Receptor-mediated endocytosis  Endocytosis: Pinocytosis Cytosol Outside cell Water molecule Solute molecule Plasma membrane 1. Solute molecules and water 2. Membrane pockets inward, 3. Pocket pinches off as molecules are outside the enclosing solute molecules and endocytic vesicle. membrane. water molecules.  Receptor-Mediated Endocytosis Clathrin Cytosol Outside cell Target molecule Receptor Plasma membrane 1. Substrates attach to 2. Membrane pockets inward. 3. Pocket pinches off as membrane receptors. endocytic vesicle.  Receptor-Mediated Endocytosis Molecules bound to Plasma surface membrane receptors pinching off Coated pit Coated pit Clathrin coat deepens Plasma membrane  Familial Hypercholesterolemia Receptor-mediated endocytosis Take up cholesterol by LDL receptor is defective Inherited disease - mutation in LDL receptor Result: high cholesterol in blood  ____________ Phagocytosis Fig. 5-20, p. 109 The Cellular Internet It’s all about communication.  Signal Transduction Pathway A signal on a cell’s surface is converted into a specific cellular response Normal Apoptosis Why is communication so important in multicellular organisms? Intercellular Chemical Messengers Controlling cell – Synthesizes specific molecule that acts as a signalling molecule to affect activity of the target cell Target cell processes signal in 3 steps: 1. Reception 2. Transduction 3. Response  Signal Transduction Surface Receptors Surface receptors – Integral membrane proteins – Recognize and bind signal Binding of a signal molecule – Induces molecular change in the receptor that activates its cytoplasmic end –  transmits the signal  Response of Surface Receptor INACTIVE ACTIVE Therefore change in function Cellular Response Pathways Signal transduction pathways – Binding of signal molecule to surface receptor triggers cellular response without entering cell – Signal relayed inside cell by protein kinases Protein kinases – Enzymes that transfer phosphate group from ATP to particular target proteins = phosphorylation  Stimulates or inhibits activities of target proteins, producing cellular response How do we balance cellular response pathways? Protein phosphatases – Reverse response – Enzymes that remove phosphate groups from target proteins – Turn off signal transduction pathway Protein Kinase Cascade Phosphorylation Transduction Cellular Response Pathways Amplification – Increase in magnitude of each step as signal transduction pathway proceeds – Each enzyme activates hundreds/thousands of proteins that enter next step in pathway – Allows full internal response when few signal molecules bind to receptors Amplification Putting it into perspective 1. What is the purpose of membranes? 2. How are they designed? 3. What are their mechanisms for selection? 4. Why do cells need to communicate? 5. What are the three main steps of communication?