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3.0 Cell Communication Recap 3.1 Cell Communication List the types of signals involved in communication and where they come from. Describe the types of signal transduction pathways that are under strong selective pressure. Explain how bacteria can use quorum sensing as an example of how signal transduction pathways influence how the cell responds to its environment. Using Epinephrine stimulation of glycogen breakdown in mammals, explain how in multicellular organisms, signal transduction pathways coordinate the activities within individual cells that support the function of the organism as a whole. Using plasmodesmata as an example explain how cells communicate by cellto-cell contact. Using neurotransmitters, explain how cells communicate over short distances by using local regulators that target cells in the vicinity of the emitting cell. Explain how signals released by one cell type can travel long distances to target cells of another cell type. Describe how different messengers bind to different signals and explain how a receptor protein is activated to transduce the signal. Describe the process of signal transduction and explain the role of second messengers. Types of Cell Signaling Direct contact: cells can receive information when their membrane contacts another cell's membrane through cell-cell recognition. This type of signaling can involve receptors recognizing cells or involve cell junctions (like plasmodesmata) connecting cells to each other. Important for embryonic development and immune response. Paracrine signaling: short range and short-lived signaling where cells secrete signals to nearby neighbors. A common example would be a growth factor. Cells can secrete growth factors to encourage nearby neighbors to grow. o Synaptic signaling: specialized nervous system signaling. Short ranged, but very fast. Electrical signals trigger the release of neurotransmitters which pass the message to a target cell. Autocrine signaling: signaling where the cell sends the signal to itself. Prevalent in apoptosis signaling, development/differentiation, and inflammatory response Short range/local plant signaling is less understood as they use different mechanisms than animals. Hormone signaling: hormones are secreted for distribution across long distances. In animals, this means the use of the circulatory system. In plants, this can mean through vessels or through gas. Hormone signaling is generally far reaching, long lasting, and slower than local signaling. Important to distinguish that hormones are used for long distance signaling. Endocrine cells can secrete hormones that travel through the circulatory system before arriving at a target cell on the other side. Direct Contact- Plasmodesmata signaling Plasmodesmata allow the direct passage of molecules between cells. So if one plant produces a signal to stimulate growth, any cell directly connected to it through plasmodesmata may also receive the same signal and produce a similar response. Thus, a plant cell may communicate to its neighbors when it is appropriate to grow by sharing its growth factors, thus coordinating a growth response throughout many cells. Quorum Sensing-sensing and responding to local population density This process is exemplified in bacteria. Quorum sensing can be described as density dependent responses. In the lecture, an example is provided using autoinducers. o When cells are in low density, these autoinducers diffuse out of the cell and so the cells do not produce much autoinducers. This results in low concentrations of autoinducers so long as population density is low. o When cells are in high density, the autoinducers stay in the cell and cause the cell to produce more autoinducers. This results in a positive feedback loop, resulting in continually high concentrations of autoinducers so long as population density is high. o By coupling these autoinducers with the expression of genes, bacteria can use autoinducers to inact density dependent responses. This also means that single celled organisms can coordinate responses as groups. Autoinduced responses will result in an entire population responding similarly. Since autoinducers are ancient in terms of evolution, it is hypothesized that autoinducers (and quorum sensing in general) may be evolutionarily significant. The ability to coordinate responses between multiple cells through local signals would have been important for early multicellular organisms. Selective Pressures on Signal Transduction Pathways A quick note; I try to be concise in these summaries but for this point, I would like to share the entire explanation that was provided to me by one of my teachers. Natural selection drives evolution towards whichever version of an organism that can best reproduce and propagate more versions of itself. When resources are scarce, this may mean natural selection drives evolution towards efficiency. Cell communication may have been selected since it allows cells to react to the environment and thus be more efficient, gathering food when it is most plentiful and conserving energy during times when it would be wasteful to expend it. Thus, we see that the idea of cell signaling would be favorable but why do we see long series of signals in the form of signal transduction pathways instead of an efficient, short, single signal from stimulus to response? Signal transduction pathways allow for a signal to be propagated/amplified. A multistep process can allow multiple signals to lead to the same response, or a single signal to lead to multiple responses. Thus, an “inefficient” route for a single task may be more efficient when you consider the flexibility that a multi-step process provides. Natural selection may therefore, have selected for a compromise between efficiency and flexibility. Signal Transduction Pathway- a series of signals that leads to a cellular response Protein Phosphorylation and Dephosphorylation o In each step of a pathway, a receptor's shape is changed in order to trigger the next step. This change in shape often comes in the form of phosphorylation. o Kinase is responsible for taking a phosphate from ATP and adding it to a molecule. Very common in signal pathways. o Phosphatase is responsible for taking a phosphate from a molecule. Used to reset pathways. o Think of Phosphorylation/Dephosphorylation as an On/Off switch. For many molecules, having an attached phosphate group turns to protein into the “on” position and a certain specific activity begins. To turn off this activity, the protein must be dephosphorylated. (In some proteins, it's reversed). Second Messengers- small molecules and ions that relay messages o G protein coupled receptor A receptor is responsible for receiving and binding to a signal. This receptor then activates a G protein the receptor is coupled with. G protein coupled receptors are responsible for activating Adenylyl cyclase. o Cyclic AMP Adenylyl cyclase converts ATP to cAMP. When a signal activates Adenylyl cyclase, the signal is passed on when ATP is converted to cAMP. cAMP is then passed on to a kinase which is activated by cAMP. Epinephrine as an Example o Epinephrine is a hormone also known as adrenaline. Start with a single Epinephrine (1 epinephrine) 1. Epinephrine binds to a G protein (102 activated G proteins) coupled receptor. 2. G protein coupled receptor activates adenylyl cyclase. 3. Adenylyl cyclase converts ATP to cAMP. 4. cAMP activates protein kinase A. 5. Protein Kinase A phosphorylates phosphorylase kinase. 6. Phosphorylase Kinase phosphorylates glycogen phosphorylase. 7. Glycogen phosphorylase finally performs the cellular response. It converts glycogen to glucose-1phosphate. (102 adenylyl cyclases) (104 cyclic AMP) (104 protein kinase As) (105 phosphorylase kinases) (106 glycogen phosphorylases) (108 Glucose-1-phosphates) o As the pathway proceeds, the signal is amplified. A single epinephrine activates 102 G proteins. 102 adenylyl cyclases will create 104 cyclic AMPs. etc. Thus, we see how a single epinephrine can amplify a signal to produce 108 glucose-1-phosphates since many proteins in the response can perform a task more than once before it is inactivated. o The important takeaway from this is that by using multiple steps, a cell can regulate a reaction in ways such as amplifying a specific response. Synaptic signaling A voltage going through a neuron causes a voltage gated channel to open, allowing Calcium ions to rush into the cell. The Calcium ions cause the cell to release neurotransmitters. The neurotransmitters travel towards its neighboring cell, on the other side of the synapse. Here, the neurotransmitter binds to a ligand gated ion channel. The ion channel opens, allowing ions to flow in and out. This ligand gated ion channel thus causes a voltage to be sent through the receiving neuron. The neurotransmitter is quickly released and the signal stops as the neurotransmitter is removed and degraded. A reminder! As this is all occurring, recall that all of these proteins work by changing shapes. Structure = function! 3.2 The Cell Cycle Explain the reasons for cell division and why cells may not divide after maturity, give examples. Describe the phases of the cell cycle and what happens to the chromosomes in each phase. Explain how DNA can fit in the nucleus of the cell with chromosome folding; describe the differences between chromatin and chromosomes. Describe the structure of a metaphase chromosome. Compare and contrast the processes of telophase and cytokinesis. Explain the differences between plant and animal cell separation. Describe how bacteria divide and how this process is different from mitosis. Describe the factors that must be present for the cell to divide. Describe the checkpoints of the cell cycle and why a cell would be placed in G0 phase. Describe the role of cyclins in cell cycle regulation. Explain the role of tumor suppressor genes / proto-oncogenes and how they can lead to cancer. Explain the evolutionary link between binary fission, mitosis, and division of various protists. Cell division: Why bother? For single celled organisms, cell division is their means of reproduction and propagating their genes. Cells that reproduce are the ones whose genes survive! For multicellular organisms, cell division allows the organism to get bigger. Larger size can mean being able to survive (by being able to obtain more food or ward off predators), reaching reproductive maturity, etc. Cells may stop dividing after maturity, especially in multicellular organisms. In multicellular organisms, cells differentiate into specific types of cells. This differentiation allows them to perform specific tasks and some of these cell types no longer need to divide. For example, the neurons in your brain! DNA packaging DNA would be very long if you stretched it all the way out. In order to fit inside the nucleus of a cell, it must be folded up. We're all familiar with the DNA double helix. The next step to DNA structure is wrapping the helix around a histone. The DNA at this point is then wrapped around to form nucleosomes. By coiling the DNA, you can condense it and make it take up much less space. Eukaryotic Cell Cycle Summary Interphase o G1 phase- gap phase; grows o S phase- synthesis; genetic material is duplicated o G2 phase- gap phase; gets ready for division o Interphase takes up most of a cell's life M Phase o Mitosis Prophase Chromatin condenses into discrete chromosomes. These chromosomes are sister chromatids joined together at centromeres. Mitotic spindle begins to form. Centrosomes move away from each other. Prometaphase Nuclear envelope fragments. Microtubules extend into nuclear area. Chromosomes continue to condense. Chromatids now have a kinetochore which attach to some microtubules. Metaphase Centrosomes now at opposite ends. Chromosomes align along the metaphase plate (an imaginary line between the centrosomes) Anaphase Cohesion proteins are cleaved so that sister chromatids can suddenly part ways. Each chromatid becomes a chromosome. The chromosomes move towards opposite ends, the cell elongates. At the end of anaphase, each of the two ends of the cell have equal halves of the chromosomes Telophase Two daughter nuclei form, one in each half Chromosomes loosen up Cytokinesis Overlaps with telophase; the cytoplasm is split and divided into two parts. The beginning of this process is marked by a cleavage furrow, which pinches the cell into two halves. The cleavage furrow is formed by a contractile ring of microfilaments. Plant cells must form a cell wall during cell division; this cell wall is sufficient to divide the cytoplasm and so cleavage as it occurs in animal cells doesn't really occur. Instead, a cell plate forms during mitosis which extends into a full cell wall. Prokaryotes go through Binary Fission Recall that bacteria do not have nuclei and that their genetic material consists of a single circular strand. Thus, their replication process is different. o 1. Chromosome replication. o 2. As replication continues, the origins of replication (of which there are now two copies) moves to opposite ends of the cell. The cell elongates. o 3. The plasma membrane grows inward and a new wall forms to separate the two sides. o 4. Two daughter cells result. Some protists that go through binary fission demonstrate a basic spindle formation. This suggests an evolutionary link between mitosis and binary fission, with this protist form a fission serving as an intermediate. Cellular control system Cells have checkpoints along their cell cycle that must be passed before the next stage may begin. There is the G1 checkpoint, the G2 checkpoint, and the M checkpoint. If a cell does not pass the G1 checkpoint, it enters a G0 phase where the cell no longer divides. Most human cells are in G0 phase. Cyclin and Cyclin dependent Kinases (cdk) o The proteins needed for the cell cycle generally stay at the same concentration throughout, but their activation changes depending on the fluctuating concentration of cyclins, which activate cdks. o Example: 1. Cyclin production starts in S phase and continues through G2 phase uninterrupted. 2. Cyclin accumulates until it reaches a high enough concentration that it binds with CDKs. When enough Cyclin-CDK complexes form, the cell can proceed through the G2 checkpoint to the next phase. 3. This Cyclin-CDK complex, we'll call MPF or maturation promoting factor... MPF phosphorylates proteins in order to promote metaphase. 4. At the end of mitosis, MPF is split. CDK becomes inactive while cyclin is degraded. 5. We return to the beginning, with no cyclin until it starts to build up again. o Each checkpoint is regulated in a similar manner with cyclins! Cancer Cancer is essentially a mass of cells that no longer divide properly. It has a large variety of causes and forms. Proto-oncogene- genes that code for regulatory proteins involved in protein growth and cell division Tumor suppressing genes- genes that code for proteins that inhibit cell division Can you see how malfunctioning versions of these genes could lead to cancer? If proteins do not inhibit cell division, then cells divide out of control. If improper regulation occurs,