Class Notes (834,026)
Canada (508,290)
Biology (2,907)
BIO1140 (688)

Cell to Cell Signalling

13 Pages
Unlock Document

Kathleen Gilmour

Topic 5: Cell-to-Cell Signalling -types of cell communication: 1) Direct -i.e.: gap junctions and plasmodesmata -involves a direct cytoplasmic link between the cells for small molecules to pass through 2) Contact -i.e.: cadherins and integrins -involve membrane proteins that recognize other elements of the cell matrix and bind to them -involves recognition and adhesion -with respect to cadherins, the 2 cells have to recognize each other because of the cadherins -what occurs in the junctions (i.e.: adherins junctions / focal junctions) affects what is going on in the cell -e.g.: for cell crawling, focal adhesions must be made and then let go again -what goes on in the cell determines what happens with the focal adhesions 3) Chemical Messengers -will be the focus of this topic Types of Chemical Messengers -vary in types -can act locally or at a distance -can be produced by different kinds of cells 1) Hormones -chemical messengers that are synthesized by cells (i.e.: specialized cells called endocrine cells) -are released into the extracellular environment -carried to a distant target cell (in the blood or extracellular fluid) -important in large, multicellular organisms where you want to integrate activities of different parts of the organism that are distant from each other 2) Paracrine Messengers -also known as paracrine agents -released by the signalling cell and act on neighbouring cells -are local mediators 3) Neurotransmitters and Neurohormones -chemical messengers that are released by neurons -neurotransmitters tend to act on the cell that is next to the neuron -neurohormones are released to act at a distance (released into extracellular fluid and act at a distance from the neuron that produced them) The Fight or Flight Response -epinephrine and norepinephrine are the chemical messengers involved -they increase heart rate, rate of respiration, blood flow to skeletal muscles, slows down digestion / urine formation, dilation of pupils -blood sugar level increases -these chemicals get the organism ready to deal with an emergency situation Steps in a Signalling System 1) Signalling Molecule (First Messenger) -excreted by the cell to the extracellular environment -acts on target cells (cells that have receptors that recognize the signal) 2) Reception -involves a ligand-binding site -only the cells with the appropriate receptor will recognize the signal; if there is no receptor, there is no effect -the receptor-signalling molecule has a unique fit which binds to the receptor in order to activate it and the signal can then be converted into a cellular response -reception may be membranous, cytosolic, or nuclear -receptors can be on the cell membrane (essential for water soluble signals since they can't penetrate the cell membrane easily), in the cytoplasm, or on the nucleus -typically, cells have a wide range of receptors and the population of receptors (proteins) is dynamic -numbers of receptors can be increased for a particular signal to get a stronger response or the number of receptors can be decreased for a particular signal to get a weaker response 3) Transduction -is the process of converting the signal into a cellular response -will cause the behaviour of the cell to change in some way 4) Cellular Response -may involve changes in gene expression which lead to changes in protein synthesis -often, these changes occur slowly -occur from hours to days to weeks -i.e.: effects of testosterone on muscle growth; the effect does not occur instantly -other responses may involve altering proteins that are already there (changes in protein activity) -i.e.: changes in transport proteins, cytoskeletal proteins, motor proteins, receptor proteins, etc.) -these responses occur quickly (from seconds to minutes) -e.g.: the fight or flight response -the responses are cell-type specific -i.e.: adrenaline has one effect on the heart but a different effect on the liver -different pathways are being turned on within the cell 5) Termination -involves the ending of the cell response -a cellular response that goes on for too long is damaging to the cell and needs to be controlled by turning off the pathway once the response has occurred -failure to turn off signalling pathways may result in problems like cancer -termination may include taking the receptors away, shutting off elements of the signal- transduction pathway, etc. Membrane Receptor Signalling Systems (Water-Soluble Messengers) -water soluble messengers interact with membrane receptors -e.g.: peptide hormones / protein hormones (insulin), environmental chemicals (things you smell or taste), small molecules (acetylcholine, amino-acid derivatives like adrenaline) -water soluble messengers do not penetrate easily into the cell and must exert their effects on cell membrane receptors -the cell membrane receptors are transmembrane glycoproteins -have a transmembrane domain -the external side of the receptorl has a ligand-binding domain where the signalling chemical binds to the receptor -the intracellular side has a domain whose activity is altered by the binding of the signal; the signal binds to the receptor, changes the conformation of the protein, and turns on the intracellular domain in order to initiate the signal transduction pathway How can we show experimentally that binding of the signal molecule to a surface receptor is what triggers the cellular response (i.e.: that the signal molecule does not enter the cell)? -you can use a marker to see if it enters the cell -you can use an analogue of the molecule that perhaps may not be related to the chemical but has the same structure and if it also triggers the pathway, it is likely to be a surface receptor that triggers the cellular response -you can inject the signal molecule into the cell and see if it produces the same response that you are interested in; if it doesn’t have the same effect, it must have exerted its effects outside the cell Membrane Receptors -respond to water soluble signalling chemicals -transmembrane proteins with a ligand-binding protein on the extracellular side -there are 3 categories of membrane receptors: 1) Ligand-Gated Channels -are receptor-channel combinations -is a protein that carries out functions as a receptor and as a channel -has a receptor site where the signalling molecule can bind -the binding of the signalling molecule changes the conformation of the protein (channel), causing it to open or close -e.g.: acetylcholine receptors -found in skeletal muscles at the end of nerve endings -they respond to the signalling molecule acetylcholine, that is released by nerve endings -acetylcholine is released by the nerve endings, bind to the ligand-binding domain of the receptor, and causes the receptor (which is also an ion channel) to open and allows Na+ ions to enter the cell which triggers the muscle contraction (which is the cellular response) -in order to stop muscle contraction, there are enzymes in the extracellular space which break down acetylcholine; this is the termination of the signalling pathway -curare (south-american blow dart poison) binds to cholinergic receptors (receptors for acetylcholine) but doesn't open the ion channel; the receptors are occupied by curare so acetylcholine cannot bind and causes paralysis 2) Enzyme-Coupled Receptors -e.g.: Receptor Tyrosine Kinases -important for regulating cell growth and proliferation -are receptors for water soluble chemicals and are therefore transmembrane proteins -have a ligand-binding domain on the extracellular side -intracellularly, the receptors have tyrosine residues and a protein kinase -a protein kinase is an enzyme that phosphorylates proteins; it adds a phosphate group to specific residues within the protein -the phosphate group comes from ATP -the protein kinase cleaves a phosphate group from ATP and it undergoes a reaction with hydroxyl groups in the amino acid residue, which covalently links the phosphate group to the amino acid residue -only Serine (Ser), Threonine (Thr), and Tyrosine (Try) have a hydroxyl group as part of the R-group and these amino acid residues are typically phosphorylated -protein kinases are specific; a tyrosine kinase is a protein kinase that specifically phosphorylates tyrosine residues -phosphorylation is important because when you add a phosphate group to a protein, phosphate carries a double charge that tends to change the conformation of the protein and therefore its function -phosphorylation is reversible; protein phosphatases are the enzymes that remove the phosphate group -the removed phosphate group can be recycled into ATP to be used for the next round of phosphorylation -phosphatases within the cell are normally active all the time and ready to de-phosphorylate proteins; kinases typically have to be turned on before they will phosphorylate a protein -this helps regulate phosphorylation, and therefore, protein function -to turn the receptor tyrosine kinase on, 2 signalling molecules must bind to 2 individual receptors and then those 2 receptors come together (dimerize) and become activated -the dimerization process activates the kinase and allows the receptor to phosphorylate its own tyrosine residues (auto-phosphorylation) -once it is auto-phosphorylated, it can then recruit and phosphorylate other proteins; this triggers the rest of the activity within the cell -receptor tyrosine kinases are often activated by growth factors (hormones that regulate cell division, cell proliferation, cell growth, and cell differentiation) -i.e.: insulin -the growth factors bind to the receptor tyrosine kinases, which dimerizes, auto-phosphorylates, and is ready to phosphorylate others and activate the pathway -one of the common pathways that the activated receptor tyrosine kinase turns on is the MAP kinase pathway (mitogen-activated protein kinase pathway) or MAPK -a mitogen is a growth factor that promotes mitosis -this pathway promotes cell division and growth by activating elements that regulate transcription (i.e.: transcription factors and transcription regulators) -going from the activated receptor to the activated transcriptional regulators involves the MAPK pathway -the activated receptor turns on a protein called Ras (a GTP-ase; a proteinthat hydrolyzes GTP) -its activity depends on whether it GTP or GDP is bound to it -it is inactive when GDP is bound to it -it is active when GTP is bound to it -Ras is activated by dropping GDP and picking up GTP -the activated Ras can then phosphorylate a MAP kinase which produces a MAP kinase cascade -the end result of this MAP kinase cascade is the activation of transcriptional regulators which then affects cell growth -expression of certain genes is controlled and the proteins produced bring about cellular responses -the end point of the MAPK pathway is the phosphorylation of a transcriptional regulator -30% of all cancers involve a problem with Ras which become constantly active and result in uncontrolled cell growth -e.g.: the co-ordinated effects of insulin -insulin is a hormone that regulates blood sugar levels through receptor tyrosine kinase pathways -high blood sugar levels = secretion of insulin (which will lower blood sugar) -insulin promotes glucose uptake into cells; in the liver, the glucose can be converted to glycogen for storage -an active, dimerized insulin receptor binds a protein called IRS-1 (insulin receptor substrate 1) -the activated receptor phosphorylates IRS-1 and can then activate several different pathways in the cell -it can activate Ras indirectly which will turn on the MAPK pathway; the genes that are activated in this case are the genes that code for enzymes involved in glycogen synthesis (i.e.: Ras will cause an increased production in the enzymes that are required to synthesize glycogen -it can indirectly activate another pathway with an Akt (protein kinase B) endpoint which will promote the insertion of glucose transporters into the cell membrane in order to increase the ability of the cell to take up glucose and will activate glycogen synthase which is the enzyme involved in synthesizing glycogen from glucose -all these actions have co-ordinated effects which promotes glucose uptake into the cell and the polymerization of that glucose into glycogen for storage; all this tends to lower blood glucose levels 3) G Protein-Coupled Receptors -involves a multi-pass receptor (has 7 transmembrane domains) that is present in the membrane -these receptors are referred to as G-protein coupled receptors -has a ligand-binding domain on the extracellular side -has a binding site for a G-protein intracellularly -activating the receptor, by having a signalling molecule bind to it, turns on the G-protein which activates an enzyme that gives a second messenger and the second messenger turns on a protein kinase cascade -2nd messengers are named by the fact that they are the messenger of the signalling molecule and is an intracellular signalling molecule; it carries out the functions in the signalling pathway of the first messenger -the signalling molecule is sometimes called the 1st messenger and is an extracellular signal -the kinases that are involved in these pathways are typically Serine and Threonine kinases (not Tyrosine kinases) -
More Less

Related notes for BIO1140

Log In


Join OneClass

Access over 10 million pages of study
documents for 1.3 million courses.

Sign up

Join to view


By registering, I agree to the Terms and Privacy Policies
Already have an account?
Just a few more details

So we can recommend you notes for your school.

Reset Password

Please enter below the email address you registered with and we will send you a link to reset your password.

Add your courses

Get notes from the top students in your class.