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BIOL 373
Vivian Dayeh

Chapter 6Monday February 20 20061236 PM Chapter 6Communication Integration and Homeostasis CelltoCell CommunicationIntroductionoOK lets start out really basicWhat are the 2 basic types of physiological signalsWhich kind is responsible for most of the information in the bodyElectrical signals changes in a cells membrane potentialChemical signals molecules secreted into the extracellular fluid ECF by cellsThis type of communication is the majority of communication within the bodyoWhat are the 4 basic kinds of celltocell communication used in the bodyTalk BRIEFLY about eachGap junctions direct cytoplasmic transfer of electrical and chemical signals between cellsContactdependent signals when surface molecules on one cell bind to surface molecules on another cellLocal communication when chemicals diffuse through extracellular fluidLongdistance communication this is done by electrical signals carried by nerve cells think action potential and chemical signals transported in the blood think hormonesGap junctions transfer chemical and electrical signals directly between cellsoTalk to me about gap junctionsSee Figure 61 pg 172The idea here is that membranespanning proteins on EACH cell called CONNEXINS bind together to create a protein channel called a CONNEXON which allows ions small molecules ATP amino acids etc to flow freely between the two cells its kind of like one big cell with 2 nucleiNote that there are different types of connexins which will form different types of connexons which in turn vary in what they allow to crossGap junctions occur in almost every cell type in the body heart smooth whateverContactdependent signals require celltocell contactoOK now whats up with contactdependent signalsAs mentioned before this is when surface molecules on one cell bind to surface molecules on anotherOne type of molecule known for its role in this process is CAM or CELLULAR ADHESION MOLECULEThis is seen in the IMMUNE SYSTEM and during GROWTH AND DEVELOPMENTParacrines and autocrines are chemical signals distributed by diffusionoWhat is the difference between a paracrine and an autocrineA paracrine is a chemical that is secreted by a cell which will diffuse to and act on cells in its IMMEDIATE VICINITYWhereas an autocrine acts on the cell that secreted itJust to make it interesting sometimes a chemical can be BOTH a PARACRINE and an AUTOCRINEoWhat is a good example of a paracrine and how does it workHISTAMINE is a paracrine because it is a chemical released from damaged cells that causes the capillaries in the immediate area of the injury to collect more white blood cells antibodies etc and also causes swellingoWhat are 2 important groups of molecules that act as paracrinesCytokines REGULATORY PEPTIDESEicosanoids LIPIDDERIVED paracrines and autocrinesElectrical signals hormones and neurohormones carry out longdistance communicationoTalk to me babyWhat is a hormoneSee Figure 62 pg 173It is a chemical signal that gets secreted into the BLOOD and thusly distributed all across the bodyIt touches MOST CELLS but only affects the ones which have receptors for itoExplain the 3 different kinds of chemical signals that a neuron can releaseFirstly there is the general term NEUROCRINE for a chemical signal released by a neuron when an action potential reaches the end of the cellDepending on what the neurocrine does it is further subclassifiedNeurotransmitters rapidly diffuse across a very short distance to another cell usually causing another action potentialNeuromodulators also diffuse to other cells but they act more slowly kind of like an autocrine or paracrineNeurohormones are when the chemical released by the neuron diffuses into the BLOOD for distributionCytokines act as both local and longdistance signalsoOK we discussed this briefly earlier but expound nowThey are amongst the most RECENTLY identified communication moleculesThey can function as autocrines or paracrines this is when they control cell development and differentiationBut they can also work just like hormones when we get stress and inflammation they are part of the immune response in being transported through the circulation just like hormones areoWhat are the crucial ways in which cytokines differ from hormonesThey act on a broader spectrum of target cells both far ones and close onesThey are NOT produced by specialized glands like hormones are cytokines are produced by all nucleated cellsThey are made ON DEMAND unlike hormones which are made in advance and just stored until needed Signal PathwaysIntroductionoWhat are the common features of a signal pathwaySee Figure 63 pg 174The signal molecule aka LIGAND or FIRST MESSENGER binds to the receptorThe ligandreceptor binding activates the RECEPTORThe receptor activates one or more INTRACELLULAR SIGNAL MOLECULES also known as SECOND MESSENGERSThe last signal molecule in the pathway initiates the synthesis of a TARGET PROTEIN or modifies an EXISTING protein to create a responseReceptors are located inside the cell or on the cell membraneoQuickly now what are the categories of signal molecules and of target cell receptorsSignal molecules are either LIPOPHILIC can dissolve in lipid or LIPOPHOBIC cannotTarget cell receptors are either INTEGRAL MEMBRANE PROTEINS in the NUCLEUS or in the CYTOSOLSee Figure 64 pg 175oWhat are the different pathways which signal molecules can followLIPOPHILIC OK these guys will go straight through the cell membrane because they can and bind to either cytosolic receptors or nucleic receptorsUsually these guys will turn on a gene and get the transcriptiontranslation machinery to start making its associated protein thus its effect is SLOWLIPOPHOBIC these guys CANNOT go through the cell membrane so they bind to receptors on the membrane surfaceThere are different kinds of membrane receptorsSee Figure 65 pg 175Ligandgated channel binding will cause it to open or closeReceptorenzyme complex binding will activate the enzymeG proteincoupled receptor binding will open an ion channel or alter enzyme activityIntegrin binding will alter the cytoskeleton somehowMembrane proteins facilitate signal transductionoExplain what signal transduction isWhich membrane receptors does this concept apply toThe idea is kind of like fine this first messenger from outside came and activated meNow what do I do to pass on the signalOr more formally the process in which an extracellular signal molecule activates a membrane receptor that in turn alters intracellular molecules to create a responseIt applies to ALL the membrane receptors EXCEPT the ligandgated ion channel because all that does is open up and let stuff in which in itself IS the passingon of the signaloExplain the concept of signal amplification and how cells do itSignal amplification some signal is made larger or amplifiedThis happens in the cell when the reception of a single first messenger molecule causes the activation of an amplifier enzyme which will create SEVERAL more molecules which in turn go and do stuffthus it is NOT a 11 ratio between each stepinstead everything has been amplifiedoState the basic pattern of a biological signal transduction pathwaySee Figure 68 pg 177An extracellular SIGNAL MOLECULE binds to and activates a proteinglycoprotein MEMBRANE RECEPTORThen the receptor turns on its associated proteins which can do a number of thingsActivate PROTEIN KINASES these guys are enzymes which phosphorylate a protein which either activates or inactivates itActivate AMPLIFIER ENZYMES these guys create SECOND MESSENGERS which do stuffThe second messengers if they are created can also do a VARIETY of thingsAlter the open state of ION CHANNELS as you may expect this will affect the cells MEMBRANE POTENTIALIncrease INTRACELLULAR CALCIUM either calcium will get let in from the OUTSIDE or we will see its release from INTRACELLULAR STORESeither way calcium can bind to proteins and change their functionCHANGE ENZYME ACTIVITY especially of protein kinases discussed earlier or protein phosphatases REMOVE a phosphate group from a proteinAnd then the ultimate result the proteins modified by calcium binding and dephosphorylation control one or more of the followingMetabolic enzymesMotor proteins for muscle contractioncytoskeletal movementRegulate gene activity and protein synthesisMembrane transport and receptor proteinsoExplain the concept of a signal cascade and how it is applicable hereThe idea is that when a first messenger hits the cell often there are many steps before the ultimate responseEach step involves the conversion of something from an inactive form to an active form which then catalyzes the conversion of another thing from inactive to active and so onhence our CASCADEReceptorenzymes have protein kinase or guanylyl cyclase activityoDont cheatWhat are the enzymes of receptorenzymesWhat happens as a resultEither we have protein kinases as the enzyme for example TYROSINE KINASE in which case a tyrosine residue of a protein will get phosphorylatedOr we can have GUANYLYL CYCLASE as the enzyme which will get activated and convert GTP to cyclic GMPMost signal transduction uses G proteinsoOK so explain how the whole Gprotein coupled receptor system works in generalWell first we have the RECEPTOR itself which is generally a MEMBRANESPANNING PROTEIN that crosses the phospholipid bilayer of the membrane SEVEN times forward and backAnd then the receptor is linked to a 3part tranducer molecule which is our G PROTEINThis thing is called a G protein because they are bound to guanosine nucleotideseither GDP or GTPWhen it is a GDP the protein is inactivated but when it gets exchanged for a GTP we get activation and the G protein takes further action either byOpening an ion channel in the membraneOr altering enzyme activitythe most common enzyme is ADENYLYL CYCLASE or PHOSPHOLIPASE CAdenylyl cyclasecAMP is the signal transduction system for many lipophobic hormonesoExplain how the G proteincoupled adenylyl cyclasecAMP system worksSee Figure 611 pg 180G proteinlinked receptors also use lipidderived second messengersoJust quickly what is the result of the Gprotein coupled PLC systemThe idea here is that the G protein activates the enzyme phospholipase C which then converts a phospholipid from the MEMBRANE called PHOSPHATIDYLINOSITOL BISPHOSPHATE into diacylglycerol and inositol triphosphateThen diacylglycerol goes and activates protein kinase C which causes more stuff to happenInositol triphosphate goes into the CYTOPLASM since it is watersoluble and causes the release of Ca from the endoplasmic reticulumIntegrin receptors transfer information from the extracellular matrixoOK so whats up with integrinsOn the outside they bind to proteins of the extracellular matrix or to ligands like antibodies and molecules involved in blood clottingWe can tell what their function is blood clotting wound repair cell adhesion and recognition in the immune response etcAnd on the inside they are bound to the CYTOSKELETON via anchor proteinsThe most rapid signal pathways change ion flow through channelsoWhy are ligandgated ion channels so FASTIts because the receptors are often located in the excitable tissues of nerve and muscleAll that needs to happen is for a ligand to bind to the gate and open it then we get ions pouring in and a change in the membrane potential and BANG stuff happensoUnderstand Figure 614 pg 182 Novel Signal MoleculesCalcium is an important intracellular signaloWhat are the 2 sources from which calcium can enter the cytosolIt can come from outside via voltagegated Ca channels or ligandgatedmechanicallygated channelsAlso it is stored in intracellular compartments such as the ENDOPLASMIC RETICULUM where its release can be induced by molecules such as the AFOREMENTIONED IP3
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