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Transcript
Cell Membrane Structure and Function Cystic Fibrosis •most common autosomal recessive disease affecting Caucasian populations – •incidence of 1 in 2000 births •Clinical features – – – – •pulmonary obstruction and infection •recurrent and persistent infections •exocrine pancreatic dysfunction •infertility, especially in males • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Diagnosis • failure to thrive -child fails to gain weight despite a good appetite • sweat test -chloride concentration greater than 60 meq/liter • life expectancy now often >30 years • this was the disease most people thought would be a good candidate for gene therapy • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Metabolic Basis of Disease • defect in a single gene on chromosome 7 that encodes a cAMP-regulated chloride channel • called Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) • resides on the apical surface of epithelial cells lining the airways, intestines, vas deferens, sweat ducts, and pancreatic ducts • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Genetics and Epidemiology • autosomal recessive • 4-5% of Americans have at least one CF allele • >900 different mutations (.F508, ~70% of CF alleles) • ~50% of the patients are homozygous for the .F508 mutation • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Consequences of Disease • Loss of CFTR function – fluid secretion is insufficient – protein portions of the secretions become viscous – results in obstruction in the ducts and eventual organ dysfunction • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Lung Disease • accounts for much of the morbidity and nearly all the mortality from the disease • bacterial infections become soon after birth, and remain difficult to stop • Pseudomonas aeruginosais the main agent in patients 18 or older • bacterial resistance to antibiotics results in mucoid coating of lungs, and subsequent decline in lung • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Cystic Fibrosis • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Membrane Functions • Isolate the cell’s contents from the external environment • Regulate traffic in and out of the cell • Communicate with other cells • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ II. Plasma membrane structure and functions The phospholipid bilayer and isolation 1. Impermeable to water-soluble and polar molecules, ions 2. Permeable to small and nonpolar molecules 3. Lipids oriented with polar heads facing out • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ tails (hydrophobic) head (hydrophilic) extracellular fluid (watery environment) phospholipid hydrophilic heads hydrophobic tails bilayer hydrophilic heads cytoplasm (watery environment) Membrane Structure and Function • Membranes are “fluid mosaics” with proteins embedded in or attached to the membrane • Proteins can move within the fluid lipid bilayer • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ extracellular fluid (outside) recognition protein receptor protein transport protein binding site phospholipid bilayer carbohydrate phospholipid cholesterol protein filaments cytoplasm (inside) • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Types of Membrane Proteins 1. Transport proteins – regulate the movement of water-soluble molecules across the membrane • Channel proteins • Carrier proteins • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Types of Membrane Proteins 2. Receptor Proteins • trigger cellular response when specific molecules bind to them Nervous system Endocrine system • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Types of Membrane Proteins 3. Recognition proteins • act as ID tags and cell surface attachment sites – the immune system • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ • • • • Key Classes of Membrane Proteins A.Transport channels-Intergral – 1.Membrane selects what substances will enter – 2.Take up molecules present in high concentration – 3 Part of protein extends through bilayer – 4.May be non polar helix beta-pleated sheets of non polar amino acids – 5.Non polar portion held within interior of bilayer – 6.Polar ends protrude from both sides of membrane B. Enzymes – 1. Chemical reactions carried out on interior surface of membrane • 2. Enzymes attached directly to membrane-carry out actions within the cell • 3. Cell surface receptors-glycoproteins, glycolipids, oligosaccharides – – – – – a. Membranes sensitive to chemical messages b. Receptor proteins on surface act as antennae-interpresurroundings c. Receptors for extra cellular signals are also single-pass anchors d. Portion of receptor that sticks outward binds with molecules e. Binding induces changes in part of protein on the inside • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ • C. Glycoproteins-MH-ID tags -recognition – a.self recognition-cells to other cells – b. Creates proteins/carb chains shaped for specific person – c. self recognition – 2. Glycolipid» a. Tissue recognition » b. Lipid/carb chain » c. Specific for each tissue » d. Blood types • D. Cell adhesion proteins – a. Cells use certain proteins to glue themselves to one another – b. Some are detachable, others are permanent • 4. Attachments to the cytoplasm-peripheral – a. Surface proteins may interact with other cells – b. Often linked to cytoskeleton by proteins • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ The Extracellular Matrix • Structure: – Glycoproteins – Collagen – Glycolipids • Functions: – Support, adhesion, movement – In Embryonic development - guides movement of cells • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Intracellular Junctions Tight junctions – Epithelial cells (surface): Seal cells together – Prevent molecules from ‘leaking’ through between cells --> Keep integral proteins in place • Adherins junctions: – Transmembrane proteins that span 2 cells – Hold cardiac cells together – May be responsible for contact inhibition • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ More junctions • Gap Junctions: permit flow of substances b/w cells flow of ions – allow all cells of heart to contract @ same time – allow muscles in uterus to contract simultaneously during childbirth • Desmosomes: patches that hold cells together – Breakdown of desmosomes may contribute to metastasis of cancer • Plasmodesmata: – Allow for continuous stream of cytoplasm b/w plant cells • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ Transport across membranes • Passive transport is a function of molecular size, lipid solubility, and size of the concentration gradient 1. Simple diffusion • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ 1 A drop of dye is placed in water. drop of dye pure water 2 Dye molecules diffuse into the water; water molecules diffuse into the dye. 3 Both dye molecules and water molecules are evenly dispersed. (a) simple diffusion (extracellular fluid) (cytoplasm) Transport across membranes Passive transport…(cont.) – 2. Osmosis • a. Isotonic • b. Hypertonic • c. Hypotonic • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ (a) selectively permeable membrane H2O free water molecule: can fit through pore sugar bound water molecules clustered around sugar: cannot fit through pore pore (b) selectively permeable membrane sugar molecule water molecule pure water bag bursts 10 micrometers (a) isotonic solution equal movement of water into and out of cells (b) hypertonic solution net water movement out of cells (c) hypotonic solution net water movement into cells Transport across membranes Passive transport…(cont.) – 3. Facilitated diffusion (b) facilitated diffusion through a channel ions proteins forming permanent hydrophilic channel channel protein (c) facilitated diffusion through a carrier amino acids, sugars, small proteins carrier protein Carrier protein has binding site for molecule. (extracellular fluid) (cytoplasm) Molecule enters binding site. Carrier protein changes Carrier protein shape, transporting molecule resumes original shape. across membrane. Transport across membranes Energy-requiring transport 1. Active transport • Ion gradients and energy production 2. Endocytosis 3. Exocytosis • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ (extracellular fluid) transport protein ATP ATP recognition binding Transport protein site site binds ATP and Ca2+ Ca2+. (cytoplasm) Transport protein Transport protein uses resumes original energy from ATP to change shape and move shape. ion across membrane. (a) pinocytosis (extracellular fluid) 1 2 3 vesicle containing extracellular fluid (cytoplasm) cell (b) phagocytosis food particle pseudopod 1 2 3 particle enclosed in vesicle secreted material (extracellular fluid) plasma membrane plasma membrane 2 3 1 vesicle (cytoplasm) 0.2 micrometer • _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________ _______________________________
