北京大学细胞生物学、物质的跨膜运输市公开课获奖课件省名师优质课赛课一等奖课件.ppt

单击此处编辑母版标题样式,单击此处编辑母版文本样式,第二级,第三级,第四级,第五级,*,本资料仅供参考，不能作为科学依据。谢谢。本资料仅供参考，不能作为科学依据。本资料仅供参考，不能作为科学依据。谢谢。本资料仅供参考!,Chapter 5,Learning Objectives:,1.Principles of membrane transport;,2.Passive transport and active transport;,3.Two main classes of membrane transport proteins:,Carriers and Channels;,4.The ion transport systems;,5.Endocytosis and Phagocytosis:cellular uptake of,macromolecules and particles.,A.The Movement of Substances Across Cell Membranes,1/90,A motor neuron cell body in the spinal cord.,(A)Many thousands of nerve terminals synapse on the cell body and dendrites.These deliver signals from other parts of the organism to control the firing of action potentials along the single axon of this large cell.(B)Micrograph showing a nerve cell body and its dendrites stained with a fluorescent antibody that recognizes a cytoskeletal protein,(green).,Thousands of axon terminals,(red),from other nerve cells(not visible)make synapses on the cell body and dendrites;they are stained with a fluorescent antibody that recognizes a protein in synaptic vesicles.,2/90,1.Principles of membrane transport,The plasma membrane is a selectively permeable,barrier.It allows for separation and exchange of,materials across the plasma membrane.,3/90,Figure11-1,The relative permeability of a synthetic lipid bilayer to different classes of molecules.,The smaller the molecule and,more important,the fewer hydrogen bonds it makes with water,the more rapidly the molecule diffuses across the bilayer.,B.The protein-free lipid bilayers are highly,impermeable to ions.,If uncharged solutes are small enough,they can move down their concentration gradients directly across the lipid bilayer by simple diffusion.,Most solutes can cross the membrane only if there is a membrane transport protein to transfer them.,Passive transport,in the same direction as a concentration gradient.,Active transport,is mediated by carrier proteins,against a concentration gradient,require an input of energy.,Diffusion of small molecules across phospholipid bilayers,4/90,Figure11-2,Permeability coefficients(cm/sec)for the passage of various molecules through synthetic lipid bilayers.,The rate of flow of a solute across the bilayer is directly proportional to the difference in its concentration on the two sides of the membrane.Multiplying this concentration difference(in mol/cm,3,)by the permeability coefficient(cm/sec)gives the flow of solute in moles per second per square centimeter of membrane.A concentration difference of tryptophan of 10,-4,mol/cm,3,(10,-4,/10,-3,L=0.1 M),for example,would cause a flow of 10,-4,mol/cm,3,x 10,-7,cm/sec=10,-11,mol/sec through 1 cm,2,of membrane,or 6 x 10,4,molecules/sec through 1 microns,2,of membrane.,5/90,C.The energetics of solute movement:,Diffusion is the spontaneous movement of material from a region of high concentration to a region of low concentration.,The free-energy change during diffusion of nonelectrolytes depends on the concentration grdient.,The free-energy change during diffusion of electrolytes depends on the electrochemical grdient.,6/90,D.Transport processes within an eukaryotic cell,7/90,2.Passive transport and active transport,A.Comparison of two classes of transport.,8/90,Figure11-7,Kinetics of simple diffusion compared to carrier-mediated diffusion.,Whereas the rate of the former is always proportional to the solute concentration,the rate of the latter reaches a maximum(,V,max,)when the carrier protein is saturated.The solute concentration when transport is at half its maximal value approximates the binding constant(,K,M,)of the carrier for the solute and is analogous to the,K,M,of an enzyme for its substrate.The graph applies to a carrier transporting a single solute;the kinetics of coupled transport of two or more solutes(see text)are more complex but show basically similar phenomena.,9/90,B.Two classes of membrane transport proteins,Carrier proteins are responsible for both the passive and the active transport.,Channel proteins are only responsible for passive transport.,10/90,Figure11-8,Three types of carrier-mediated transport.,The schematic diagram shows carrier proteins functioning as uniports,symports,and antiports.,11/90,Carrier proteins bind one or more solute molecules on one side of the membrane and then undergo a conformational change that transfer the solute to the other side of the membrane.,12/90,The carrier protein,the Glucose transporter(GluT1)in the erythrocyte PM,alter conformation to facilitate the transport of glucose.,Facilitate diffusion:Protein-mediated movement,movement down the gradient,13/90,Most of the channel proteins are ion channels,including three types,with ion channels that they can be opened and closed,14/90,Figure 11-36.A model for the structure of the acetylcholine receptor.,Five homologous subunits(a,a,b,g,d)combine to form a transmembrane aqueous pore.The pore is lined by a ring of five transmembrane a helices,one contributed by each subunit.In its closed conformation,the pore is thought to be occluded by the hydrophobic side chains of five leucines,one from each a helix,which form a gate near the middle of the lipid bilayer.The negatively charged side chains at either end of the pore ensure that only positively charged ions pass through the channel.Both of the a subunits contain an acetylcholine-binding site;when acetylcholine binds to both sites,the channel undergoes a conformational change that opens the gate,possibly by causing the leucines to move outward.,15/90,电压门控离子通道：铰链细胞失水,应力激活离子通道：2X10,13,N，0.04nm,16/90,3.Active transport:Carrier protein-mediated movement up the gradient,A.This process differs from facilitated diffusion in two crucial aspects:,Active transport,maintains the gradients,for potassium,sodium,calcium,and other ions across the cell membrane.Always moves solutes up a concentration or electrochemical gradient;,Active transport,couples,the movement of substances against gradients to,ATP hydrolysis,.i.e Always requires the input of energy.,17/90,B.Cells carry out active transport in three main ways,Couple,the,uphill,transport of one solute across membrane to the,downhill,transport of another.,Couple,uphill,transport to the hydrolysis of,ATP.,Mainly in bacteria,couple,uphill,transport to an input of energy from,light,.,18/90,C.Direct active transport depends on four types of transport ATPases,The,four classes,of ATP-powered transport proteins:,“P”,type stands for,phosphorylation,;,ABC(ATP-binding Cassette)superfamily,bacteriahumans.,Two transmembrane(T)domains and two cytosolic ATP-binding(A)domains,19/90,The Na,+,-K,+,ATPase,-A coupling active transport to ATP hydrolysis.,The Na,+,-K,+,ATPase requires K,+,outside,Na,+,and ATP inside,and is inhibited by ouabain.,The ratio of Na,+,:K,+,pumped is,3:2,for each ATP hydrolyzed.,The Na,+,-K,+,ATPase is a,P-type,pump.This ATPase seruentially,phosphorylates and dephosphory-lates,itself during the pumping cycle.,The Na,+,-K,+,ATPase is found,only in aniimals,.,20/90,The active transport of Na,+,/K,+,ATPase is used to maintains electrochemical ion gradients,and thereby maintains cells excitability.,The Na,+,/K,+,pumo is required to maintain osmotic balance and stabilize cell volume,The biological functions of Na,+,/K,+,pump,forming a phosphorylated protein intermediate,21/90,A Model Mechanism for the Na,+,/K,+,ATPase,22/90,Other P-type punps:including H,+,and Ca,+,ATPases,and H,+,/K,+,ATPases,Plant cells have a,H,+,-transporting plasma membrane pump,.,This,proton pump,plays a,key role,in the secondary transport of solutes,in the control of cytosolic pH,and possibly in control of cell growth by means of acidification of the plant cell wall.,Ca,2+,pump:Ca,2+,-ATPase present in both the plasma membrane and,the membranes of the ER.It contain 10 transmembrane,helices.,This Ca,2+,pump functions to actively transport Ca,2+,out of the,cytosol into either the extracellular space or the lumen of the ER.,H,+,/K,+,ATPases(epithelial lining of the stomach):which secretes a solution of,concentrated acid(up to 0.16N HCl)into the stomach chamber.,23/90,The V-type pump:utilize the energy of ATP without,forming a phosphorylated protein intermediate.,Vacuolar(V-type)pump actively transport H,+,across the membranes of cytoplasmic organelles and vacuoles.,They precent in lysosomes,secretory granules,and plant cell vacuoles,have also been found in the plasma membranes of a variety of cells(kidney tubules).,24/90,4.Indirect active transport is driven by Ion gradients-Cotransport,A.Sugars,amino acids,and other organic molecules into cells:,The inward transport of such molecules up their concentration gradients is often coupled to,and driven by,the concomitant inward movement of these ions down their electrochemical gradients:,Animal cells,-,Sodium ions(Na,+,/K,+,ATPase),Plant,fungi,bacterium,-,Protons(H,+,ATPase),Gradients created by active ion pumping store energy that can be coupled to other transport processes.,25/90,The difference between animal and plant cells to absorb nutrients,26/90,B.Cotransport:Symport and antiport,Na,+,-linked symporters import amino acids and glucose into many animal cells,Na,+,-linked antiporter exports Ca,+,from cardiac muscle cells,Medicine,Ouabain and digoxin increase the force of heart muscle contraction by inhibiting the Na,+,/K,+,ATPase.Fewer Ca,+,ions are exported,27/90,5.Endocytosis:Large molecules enter into cells,A.Endocytosis,imports extracellular molecules dissolved or suspended in fluid by forming vesicles from the plasma membrane,Bulk-phase endocytosis,does not require surface membrane recognition.It is the nonspecific uptake of extracellular fluids.,Receptor-mediated endocytosis(RME),follows the binding of substances to membrane receptors.,28/90,B.Phagocytosis:The uptake of large particles,Including:macromolecules,cell debris,even microorganisms and other cells.,Phagocytosis is usually restricted to specialized cells called,Phagocytes.,Phagocytosis is initiated by cellular contact with an appropriate target.,Phagocytosis may be stimulated by the opsonins,Phagocytosis is driven by contractile activities of MF.,29/90,C.Receptor-mediated endocytosis,30/90,31/90,Structure of a clathrin coated vesicle,32/90,Model for the formation of a clathrin-coated pit and the selective incorporation of integral membrane proteins into clathrin-coated vesicles,33/90,The endocytic pathway is divided into the early endosomes and late endosomes pathway,Materials in the early endosomes are sorted:,Integral membrane proteins are shipped back to the membrane;,Other dissolved materials and bound ligands,Multivesicular body(MT mediated transport),the late endosomes.,Molecules that reach the late endosomes are moved to lysosomes.,34/90,6.,Exocytosis,Constitutive exocytosis pathway,Regulated exocytosis pathway,35/90,36/90,37/90,38/90,7.Membrane Potentials and Nerve Impulses,K,+,gradients maintained by the Na,+,-K,+,ATPase are responsible for the resting membrane potential.,Resting state:All Na,+,and K,+,channels closed.,Depolarizing phase:Na,+,channels open,triggering an action potential.,Repolarizing phase:Na,+,channels inactivated,K,+,channels open.,Hyperpolarizing phase:K,+,channels remain open,Na,+,channels inactivated.,B,.The action potential:The changes in ion channels and membrane potential.,39/90,The sequence of events during synaptic transmission:,Excitable membranes exhibit“all-or-none”behavior.,Propagation of action potentials as an impulse.,40/90,Chapter 5,B.Cell Signaling,Learning Objectives:,1.,Some of the basic characteristics of cell signaling,2.The types of signal molecules,receptors,molecular switches and effectors;,3.The different signal transduction pathways;,4.The convergence,divergence,and,cross talking,between different signaling pathways.,41/90,1.Overview of cell signaling,A.Some of the basic characteristics of cell signaling,Cell must respond appropriately to external stimuli to survive.,Cells respond to stimuli via cell signaling,42/90,Recognition of the stimulus by a specific plasma membrane receptor.,Transfer of a signal across the plasma membrane.,Transmission of the signal to effector molecules within the cell,which causes a change in cellular activities.,Cessation of the cellular response due to inactivation of the signal molecule.,Signal transduction pathways consist,of a series of steps,signal magnification,43/90,Each cell is programmed to respond to specific combinations of exreaceluular signal molecules,44/90,Different cells can respond differently to the same extracellular signal molecule,Figure15-9,The same signaling molecule can induce different responses in different target cells.,In some cases this is because the signaling molecule binds to different receptor proteins,as illustrated in(A)and(B).In other cases the signaling molecule binds to identical receptor proteins that activate different response pathways in different cells,as illustrated in(B)and(C).In all of the cases shown the signaling molecule is,acetylcholine,(D).,45/90,A cell can remember the effect of some signals,after the signal has disappeared.,(Ca,2+,),Protein kinase activited by Ca,2+,to,phosphorylate itself and other proteins,the autophosphorylation keeps the kinase active long after Ca,2+,levels return to normal,providing a memory trace of the initial signal.,Transient extracellular signals often induce much longer-term changes in cells during the development of a multicellular organism.They usually depend on self-activating memory mechanisms that operate further downstream in a signaling pathway,at the level of gene transcription.,46/90,B.The forms of cell communication-Different types of chemical signals can be received by cells,Gap junction,47/90,C.Signal Molecules and Receptors,signal molecules:,Lipid-soluble hormones,Water-soluble hormones,nitric oxide(,NO)and carbon monoxide(CO)as cellular messengers,48/90,Receptors include three classes:glycoproteins,49/90,D.Two types of intracellular signaling proteins that act as Molecular Switches,Phosphorylation and dephosphorylation via protein kinases and phosphatases.Thereby stimulating or inhibiting the activities,GAPs inactivate G-protein;GEFs activates G-protein;GDIs(guanine nucleotide-dissociation inhibitors)maintain the G-protein inactive.,50/90,2.Signal transdution mediated by the receptors within cells,A.Some small hydrophobic hormones(steroid hormones)whose receprors are intracellular gene regulatory proteins.,51/90,Figure15-13,Early primary response(A)and delayed secondary response(B)that result from the activation of an intracellular receptor protein.,The response to a steroid hormone is illustrated,but the same principles apply for all ligands that activate this family of receptor proteins.Some of the primary-response proteins turn on secondary-response genes,whereas others turn off the primary-response genes.The actual number of primary-and secondary-response genes is greater than shown.As expected,drugs that inhibit protein synthesis suppress the transcription