Cell Bio Module IV
Cell Bio Module IV BIOL 541
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This 13 page Study Guide was uploaded by . Notetaker on Tuesday August 11, 2015. The Study Guide belongs to BIOL 541 at Kansas State University taught by Dr. Stella Lee in Fall 2014. Since its upload, it has received 76 views. For similar materials see Cell Biology in Biology at Kansas State University.
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Date Created: 08/11/15
Module IV Chapter 13 A Cells a Neurons send and receive electrical impulses i Cell body includes nucleus and other endomembrane complonents ii Dendrites receive signals iii Axons conducts signals 1 Cytosol within axon axoplam 2 Surrounded by myelin sheath a lnsulates segments of axon separates the nodes of Ranvier 3 Nerve tissue composed of bundles of axons 4 Motor a Forms multiple branches that erminate called synaptic boutons b Junction between nerve cells called synapse b Glial cells i Microglia ght infections Oligodendrocytes form myelin shealth in CNS iii Schwann cells form myelin shealth in PNS iv Astrocytes form bloodbrain barrier c Membrane potentials fundamental property of all cells i Resting cells at rest have negative charge on inside and positive on outside 1 Cytosol coantains potassium as its main cation due to action of NAK pump 2 Potassium ions will diffuse out of cells toward region of low concentration NA ions in 3 Counterions one neg followed by one pos a K ions serve as counterions for trapped anions outside of cell NA is main cation with Cl as its counterion ii Electric potential 1 Oppositer charged ions fo flow back toward each other vo age 2 When oppositely charged ions are moving toward each other current is owing iii Equilibrium chemical gradient sis balanced iv Nerst equation math relationship between ion gradient and equilibrium potential EX RTzF nxoutxin v Goldmann equation gradients of several different ions look up equannHJ vi NaK pump 1 3 Na out 2K in 2 Cl crosses membrane together with permeable cation to make membrane more negative hyperpolarization vii Electrical excitability nerve muscle and certain other exhibit this Viii xi xii xiii 1 Have voltagegated channels a Channels potassium are multimeric composed of 4 protein subunits b Sodium channels are monomeric four separate domains c Channel specificity go thru lter all channels are either open or closed no partial opening d Voltage sensor responding to voltage change e lnactivation caused by inactivation particle that inserts in opening of channel 2 Action potential electrically excititable cells certain stimuli trigger rapid set of changes in membrane potential a Resting potential NA and K closed b Depolarizing phase when receive stimulation resting potential chances and Na channels open c Repolarizing when going back to regular potential K channels open amp NA closed d Hyperpolarizing reaches lower than normal resting potential K channels open and NA channels reactivated e Absolute refractory sodium channel cannot be activated f Relative refractory Na is not inactivated g Threshold potential initiates an action potential which is brief h Propagation travels thru membrane thru channels along axon i Action potential propagated along axon without losing strength starts in dendrites Voltage ion channels integral proteins that form ionconduction pores 1 Channels respond to changes in voltage across membrane Ligandgated ion channels open when ligand binds to channel Patch clamping records currents passing thru individual channels Hodgkin cycle positive feedback loop of depolarization Change in ion concentrations 1 Na amp K hardl change at all neuronal activity can lead to sig change in ions Syelin sheath electrical insulator surrounding axon formed by oligodendrites 1 Consequences decreases ability of neuronal membrane to retain electric charge a Nerve impulses can spread father and faster 2 Action potential are renewed at nodes of Ranvier they jum from one node to the next called saltatory propagation d Synaptic transmission i Electrical synapse two neurons connected with gap junctions speedy ii Chemical synapse two neurons connected via cell adhesion two plasma membranes separated by synaptic cleft converted to chemical signal carried by neurotransmitter 1 Neurotransmitter stored in synaptic boutons a Diffuse across cleft and bind to receptors b Excitatory receptors cause depolarization of postsynaptic neuron c Inhibitory receptor cause the postsynaptic cell to hyperpolarize d Quali cations i Elecit appropriate response when introduced to synaptic cleft ii Be released at right time when presynaptic neuron is stimulated iii Occur naturally in presynaptic neuron e Acetylcholine most common neuro outside the CNS and for muscularjunctions excitatory i Synapses that use this are called cholinergic synapses f Catecholamines dopamine norepinephrine epinephrine i Derivates of tyrosine iii Calcium levesl stimulate secretion of nuerotransmitters 1 Increase in CA due to opening of calcium channels a Vesicles are mobilized for rapid release b Or fuse with plasma membrane c Bound by synaptotagmin undergoes conformational change and promotes t and vsnares to interact efficiently d Neurotoxins tetanus amp botulism interfere with docking and release at active zone e Kissand run exocytosis vesicle temporarily fuses with membrane release neurotransmitter then reseal iv Neurotransmitter receptors 1 Ligant ionotropic receptors a Nicotinic acetylcholine receptor binds ligatn gate Na channel i Two acetylcholine bind receptor opens and lets Na rush into cell causing depolarization ii Forms rosettelike particles about 8nm across consists of 4 kinds of subunits iii Plays role in transmitting nerve impulses to muscle b GABA ligant gatedbut when opened allows Cl ion in cells cuases hyperpolarization of receiving cell amp decreased likelihood that action potential will be generated 2 Metabotropic receptors receptors that exert their effects indirectly via a system of messengers 3 Must be inactivated shortly after their release a Removed from snaptic cleft by degradation i Hydrolyzes b Neurotransmitter reuptake pumps back into presynatptic cell by active transport c Some antidepressant druge act by blocking reuptake thus prolong response v Nerve signals 1 Changes in potential due to neurtotransmitter binding are called postsynaptic potentials a Cause excitatory or inhibitory postsynaptic potentials IPSP Chapter 14 A Chemical signals a Hormones endocrine signals long distance b Local mediators short distance paracrine signals i Autocrine act on the same cell ii Juxtacrine require cellcell contact c Second messengers molecules or ions that relay signals from one location to another i Ability of cell to respond to liganereceptor binding by altering its behavior or gene expression is signal transduction ii Receptorligantinteractions 1 Receptor affinity number of receptors occupied 2 Dissociation constantKd free ligand needed to produce a state in which half the receptors are occupied 3 Receptors with high ligant af nity have low Kd and vice versa 4 Receptorligant interactions can be affected by coreceptors on cell surface they help to facilitate receptorligand interaction via physical interaction with receptor iii Receptor downregulation 1 Receptors occupied fro prolonged periods cell adapts to no longer respond to ligand a Receptormediated endocytosis cells reduce the density of receptors on their cell b Desensitization alteration to the receptor that lower its af nity for the ligand common method of desensitization is phosphorylation iv Agonist drugs that activate the receptor they are bound to v Antagonist bind receptors without triggering a change and prevent the naturally occurring messenger from activating the receptor vi Signal integration cells exposed to multitude of signals so they must integrate theses signals to produce appropriate responses 1 Single receptor can activate multiple pathways multiple pathwyas can converge onto same molecules d Signal amplifications multiplication of the effect of signal e G protein linkedreceptors i Ligand binding causes a change in receptor conformation that activates a particular G protein guanine binding 1 Structure seven transmembrane a helices extracellular portion has messengerbinding site 2 Structure inactivation depend on whether they are bound to GTP OR GDP a Have 3 receptors a B gamma a is largest and binds to GDP AND GTP b When it binds to GTP it detaches from G B amp gamma c Then it inhibits target proteins initiating signal transduction most important being second messengers 3 Protein linked receptors can be regulated via phosphorylation and carried out by G proteinlinked receptor kinases ii Glinked Receptors largest family of cell surface receptors 1 Olfactory sense of smell 900 genes in human iii G inactivation everything I wrote in abc above only GTPase activating proteins are important regulators of G protein function iv Disruption of G protein signals causes diseases 1 Cholera vibrio cholera colonizes gut it secretes cholera toxin toxin modi es Gs so that it cannot hydrolyze GTP 2 Whooping cough bordetella pertussis acts on Gi so that it can no longer inhibit adenylyl cyclase causes accumulation of uid in lungs and persistent cough B cAMP function a main target protein kinase A PKA which it regulates by separating the regulatory and catalytic subunits i PKA composed of two subunits with no cAMP subunit inhibit catalytic activity ii cAMP activates protein by binding to subunits causing a change conformation iii subunits detach they are now activated and can target proteins in cell b adenylyl cyclase pathway pathway which describes G protein pathway with a B amp gamma proteins when they are separated a attaches to adenylyl cyclase with a cAMP i this releases a phosphate then adenylyl cyclase detaches a and CAMP is turned into amp C pLC pathway a b receptor is activated by binding of ligand complex associates with G protein causing displacement of GDP by GTP i GTP complex then binds to phospholipase C activating it and causing cleavage of PlP3 to lP3 and DAG 1 lP3released into cytosol triggers calcium release a Calciumsensitive dyes can be used to demonstrate importance of calcium release treat cells with calcium ionophores results in release of calcium in absence of stimulus further implicates calcium as intermediary in lP3 signaling b Ca concentrations plays essential role in regulating variety of cell functions maintained at low levels in cytosol through calcium ATPases in PM and ER c Increase in Ca ions can cause lP3 and ryanodine receptors channels to open allowing Ca into cytoplasm d Ca binding in effector proteins i Protein calcodulin mediates calcium activated processes in cell 1 Structure like arm with hand at each end each binds two Ca when concentration is 1 uM 2 Function when two Ca bind the protein changes and forms the calciumcalmodulin complex 3 Now this complex can bind proteins by wrapping around the binding site Protein kinaseassociated receptors i Ligand binding stimulates kinas activities signaling is transmitted thru phosphorylation cascade kinases are either tyrosine or serinethreonine kinases ii Growth factors 1 Messengers in serum that stimulate growth a Serum uid after blood has clotted contains large amounts of plateletderived growth factor PDGF i PDGFreceptor tyrosine kinase ii Several growth factors stimulate receptor tyrosine kinases insulin broblast epidermal nerve iii Autophosphorylation 1 Tyrosine kinases trigger chain of events in cell that culminate cell growth proliferation specialization a Consists single polypeptide chain with one transmemraen segment vi vii Viii i Extracellular part contains ligandbinding domain ii Cytosolic side tyrosine inase domain b Receptors dimerize upon ligand binding and phosphorylate each other phosphorylate same type of receptor as themselves called autophosphorylation Nonreceptor tyrosine kinases binds to receptor and is activated in response to ligand binding Receptor initiates signal transduction cascade using RAS and MAP 1 Phosphorylated receptor recurits cytosolic proteins GRBZ 2 Cytosolic proteins recognize phosphotyrosine and nearby residues a One such domain is called SH2 domain because residues are similar to sequences on src 3 GRBZ recruites 505 a guaninenucleotide exchange factor GEF for Ras 4 Activated SOS stimultea Ras to release GDP and acquire ATP 5 Ras triggers a series of phosphorylations a First protein phosphorylated is Raf a kinase which then phosphorylates ser and thr in a kinase called MEK b MEK phosphorylates ser thr residues in MAP kinases c And then nally MAP phosphorylate transcription factors that regulate gene expression in nucleus d Then GAP deactivates Ras thru hydrolysis Rasimportant in regulating frowth of cells small monomeric G protein 1 Can bind GDP OR GTP but are active only when bound to GTP 2 Requires assistance from guaninemucleotide exchange factor called 505 to acquire a GTP molecule Tyrosine kinases can also activated phospholipase Cy leading to production of lP3 amp DAG 1 Phospholipase Cy in this case contains an SH2 domain and must bind to receptor Scaffolding complexes signaling pathways that are assembled into large multiprotein complexes Mutations 1 Dominant negative mutant receptors overrides normal function 2 Constitutively active mutations cause receptor to saty on all the time Other growth factors 1 Serinethreonine kinases bind transforming growth factor B a b c d e TFGB signaling begins with growth factor binds the transmembrane receptor Type II receptor phosphorylates type 1 receptor Recruitement of anchoring protein and RSmad complex RSmad phosphorylation and binding to Smad4 RSmad and Smad4 complex entering nucleus to regulate gene expression 2 Disruption leads to cancer can have no active growth factors or too many growth factors c Hormone signaling i Adrenergic hormones epinephrine amp norepinephrine ght or ight 1 Bind receptors a amp B 2 Alpha activates PLC pathway contraction of smooth muscle 3 Beta activates CAMP pathway relaxation of smooth muscles 4 Glycogen degradation begins when epinephrine moecues binds to B adrenergic receptor on liver or muscle cell a b CAMP also stimulates inactivateion of enzme system responsible for synthesis of glycogen PKA also phosphorylates glycogen synthase and inactivates it ii Insulin signaling 1 Specialized cells in pancrease caed islets of Langerhands secrete two peptide hormones that regulate normal glucose levels a b D GIucagonacts to increase blood glucose thru glycogen breakdown nsuin reduces blood glucose eves by stimulating uptake into muscle and adipose cells and stimulating glycogen synthesis wh Diabetes type 1 cells cannot produce insulin anymore inject insulin Type II has insulin ces cannot respond properly Signaling i Insulin binds receptor tyrosine kinases which have two a and two B subunits 1 nsuin binds a subunits B subunits phosphorylate insulin receptor substrate 1 2 This recruits GRB2 acivated Ras pathway 3 Can also bind P3K which converts PP2 to PP3 a PlP3 binds protein called Akt recruits glut4 which uptakes glucose b Also glycogen synthase activated glycogen production 2 Steroid hormones lipid signaling molecules act primarily in nucleus not cell surface Chapter 17 A Cellcell recognition a Adhesion receptors attach to one another many are transmembrane adhesion proteins are continuously recycled i Internalized by endocytosis ii New protein is deposited by exocytosis b Classes i Immunoglobulin lgSF wellorganized loops similar to those of immunoglobulins 1 Ex NCAM ii Cadherins require Ca for binding have series of similar domains on extracellular domains 1 Five repeats on EC domain zip together 2 Important roles in embryonic development 3 Functions epithelialmesenchymal transition EMT breakdown of epithelium into loosely organized mesenchyme cells is accompanied by changes in cadherin expression 4 Can result in cancer cancer cells stop expressing cadherins result cancer spreads by metastasis iii Selectins bind carb groups on cell surface 1 Many plantanimals secrete lectins which promote cell cell adhesion by binding to sugars at outer cell surface 2 Selectins link leukocytes with patelets or celllining blood vessels a L selectin on leukocytes P on platelets E on blood vessels b Stable leukocytes at the site of in ammation are mediated by integrin amp ICAM c Blood tpes i ABO blood group involves differences in carb attached to a glycoplipid on surface of RBC ii Antigen A GalNA 3 Gal AB both 0 none iii Antibodies A aGal B AGalNac AB none Oboth iv lntegrins cell surface receptors that bind ECM constituents c Interactions i Hemophilic cadherins and lgSF interact with identical recpotrs on surfaces they adhere to ii Heterophilic selectins and integrins interact with different types of receptors djuncUons i Apical polar side basolateral nonpolar ii Adhesive link cells together enabling them to function as unit 1 Anchor to cytoskeleton to cell surface and have intracellular attachment proetins on inside and cadherins on outer 2 Types a Adherens junction epithelial cells space 25nm i Continuous belt that encircles cell near apical end of lateral membrane ii Attaches between cell surface and cytoskeleton iii Bind to cadherin on outside iv Uses micro laments a catenin B catenin to bind action to cadherins v Some pathwogens make sue of adhesion proteins to infect host cells b Desmosomes button like points of strong adhesion between adjacent cells in tissue intermediate C laments 1 2 3 Abundant in skin heart muscle neck of uterus Space between two membranes desmosome core which consists of desmosomal cadherinsdesmocollin desmoglein All called desmosome plaque Tight no space between them form continuous belt around apica ends of lateral surfaces on each cell 1 2 3 4 5 Fused ridges eliminate intercellular space and seal junction Paracellular transport junction allows passage of molecules from EC uid Paracellular barrier junction blocks passage of other molecules in EC uid Act as gates amp fences blocks uids ions lateral movement within membrane of lipids and proteins Contains jAMS immunoglobulins amp claudins form tight seal d Gap junctions communications between two cells very small gap i Main receptor connexins space 23 nm ii Exchange of ions and molecules between cells B Extracellular matrix animal cells a Structural proteins collagens elastins strength and exibility i Collagenmost abundant forms tibers 1 Rigid triple helix of intertwined polypeptides 2 Unusual AA compositions glycine dydroxylysine hydrosyproline 3 Fibers visible in ECM a Three chains assemble in ER procoagen triple helix collagen molecule then bril i Stability reinforced by H bonds b 15 types of coagnes that are tissue speci c ii Elastins stretchable elastic bers 1 Rich in glycine amp proline crosslinked between lysine residues iii Collagen amp elastins enmeshed in gellike network of proteoglycans 1 Glycosaminoglcnas GAGS large carbs with repeating disaccharide units a Common types chondroitin sulfate keratin sulfate hyauronate b Has one amino sugar other sugar is usually sugar acid amino sugar usually has sulfate groups attached c Hydrophilic amp neg charged they attrace water and cations to form gelatinous matrix 2 Proteoglycans of GAG chains attached along length of core protein a In cartilage numerous proteoglycans become attached to long molecules of hyauronate i Exception that occurs both as backbond and free molecule iv Adhesive glycoproteins anchor cells to ECM 1 Multiple domains a Laminins i Mainly found in basal amina thin sheet of specialized extracellular material 1 Basal lamina underlies epithelial cells contain type IV collagen proteoglycans laminins and other glycoproteins 2 Structure 3 long polypeptides aB gamma disul de bonds hold polypeptides togheter in shape of cross 3 Enzymes that alter lamina matrix metalloproteinases degrade ECM locally a Important for leukocytes to invade injured tissues and may be factor in cancer cell invasiveness b Fibronectins i Two polypeptides disul de bond link together ii Several domains bind one or more ECM macromolecules inclusind several types of collagen heparin and brin iii Other domains recognize and bind cell surface receptors via RGD arggy asp sequence iv Effects on cell movemtn and blood clotting 1 Once attached to bronection cell atten and cytoskeletons align with bro on outside 2 Many kinds of cancer cells do not produce rbronectin 3 Soluble form plasma bronectin which promotes blood clotting because it has domains for binding brin the clotting proteins can attach blood platelets to brin as clot forms Proteinpolysaccharide complexes proteoglycans provide matrix in which structural molecules are embedded Adhesive glycoptorieins bronectins and laminins allow cell to attach to matrix lntegrins large family of cell surface receptors that bind to bronections or laminins i Integrate with cytoskeleton with ECM 1 Consists of a amp B 2 Speci ty binding depends on a subunit aSBl a6Bl Focal adhesions broblasts attach to ECM molecules via focal adhesions i Contains integrins that interact with bundles of actin laments via talin vinculin and actinin Hemidesmosomes found in epithelial cells contain a6B4 integrin which are attached to keratin in this case i Linker proteins form dense plaque connecting integrins to cytoskeleton 1 Membranes of plakin famil are linker proteins plectin attaches keratin laments to integrins Signaling integrins can signal quotinside out signalingquot signals such as growth factor that lead to MAP kinas activation can induce integrin clustering i quotoutside in signalingquot integrins can also act as receptors that activated intracellular signaling C Plasmodesmata cytoplasmic channels thru opening in cell wall allowing cytoplasmic continuity between two adjacent cells a Desmotubule single tubular structure lies in channel of plasmodesma cone ted to ER b Annulus ring of cytoplasm between the desmotubule and membrane lining the plasmodesma
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