Prokaryotic Signaling

Prokaryotic signaling: 1. Quorum sensing: communication among bacteria that leads to a response only when there are a high number of bacteria present a. Prokaryotic cells are both the signaling cell and the target cell b. Production: Bacteria produce small chemical signaling molecules called autoinducers. c. Release: The bacteria release the autoinducers into their environment. d. Recognition: The autoinducers are recognized by receptors on the bacteria when they reach a certain concentration. 2. Prokaryotes communicate among themselves to achieve a greater effect as a population Eukaryotic Signaling: 1. Cellular communication responsible for cellular response a. Fight or flight response: i. Caused by the release of adrenaline ii. Cells have adrenaline receptors and changes cellular movement Signaling pathways: 1. Cell to cell communication is critical for function and survival of cells a. Responsible for growth and development of multicellular organisms 2. Direct contact (juxtracrine signaling) : a. Communication through cell junctions i. Connect interiors of two cells ii. Transfer ions and molecules directly into the interior of another cell b. Occur in all four types of tissues (connective tissue, epithelial tissue, muscle tissue, and nervous tissue) c. Signaling substances and other materials dissolved in the cytoplasm can pass freely between adjacent cells. i. Animal: Gap junction ii. Plant cell: Plasmodesmata 1. Size of opening bigger than gap junction 2. Creates a continuous space between cells iii. d. Eg. Immune cells: Antigen (protein) presenting cells (APCs) communicate to T cells through direct contact i. T cells mature and form helper T cells and cytotoxic t cells 3. Local regulators: a secretion cell will release chemical messages (local regulators/ligands) that travel a short distance through the extracellular fluid a. The chemical messages will cause a response in a target cell – move by diffusion b. Reaches target cell faster but shorter-lived effects c. Paracrine signaling secretory cells release local regulators (ie growth factors) via exocytosis to adjacent cells i. d. Synaptic signaling occurs in animal nervous system i. Neurons secrete neurotransmitters: diffuse across the synaptic cleft space between the nerve cell and target cell ii. Helps impulse transmitting 1. e. Autocrine signaling: cell secretes a ligand. i. Ligand then binds to a receptor on the cell that secreted the ligand ii. Cell signaling ot its self to generate a response iii. Eg. Cancer cell: releases its own growth hormones to stimulate cancer cell growth iv. A part of quorum signaling 4. Long distance signaling (endocrine signaling): a. Animals and plants use hormones for long distance signaling: i. Plant: release hormones that travel it the plant vascular tissue (xylem and phloem) or through the air to reach target tissues ii. Animals: Use endocrine signaling 1. Specialized cells release hormones into the circulatory system where they reach target cells iii. Eg. Insulin: released by the pancreas into the bloodstream where it circulates through the body and binds to target cells Cell signaling: 1. Reception: Ligand binds to receptor a. Reception: The detection and receiving of a ligand by a receptor in the target cell b. Receptor: Macromolecules that binds to a signal molecule (ligand) i. All receptors have an area that interacts with the ligand and an area that transmits a signal to another protein ii. Binding between ligand and receptor is highly specific – shape and charge iii. Contains ligand specific binding domains iv. Bind to ligand through weak, noncovalent bonds 1. Allow for termination of communication when necessary c. When a ligand binds to the receptor, the receptor activates (via a conformational change) i. Allow the receptor to interact with other cellular molecules ii. Initiate transduction signal iii. Receptors can be in the plasma membrane or intracellular d. Plasma Membrane Receptors: i. Most common type of receptor involved in signal pathways ii. Binds to ligands that are polar, water soluble, and large iii. Examples: G protein coupled receptors (GPCRs) and ligand gated ion channels e. Intracellular receptors: i. Found in the cytoplasm or nucleus of target cell ii. Bind to ligands that can pass through the plasma membrane (hydrophobic) 1. Eg. Steroids and thyroid hormones and gasses like nitric oxide f. Signaling molecule: a cell that responds to the stimulus and release signaling molecules g. Target cell: has receptors that bind to the signaling molecules 2. Transduction: the conversion of an extracellular signal to an intracellular signal that will bring about a cellular response a. Requires: a sequence of changes in a series of molecules known as a signal transduction pathway b. Help the cell choose an appropriate response c. Signal transduction pathway regulates protein activities through: i. Phosphorylation: by the enzyme protein kinase: relays signals inside the cell ii. Dephosphorylation: by the enzyme protein phosphatase shuts off pathways d. During signal transduction signal is amplified i. Signaling cascade: a process in which one molecule activates multiple molecules to amplify the cellular response ii. Second messengers: small, non-protein molecules and ions help relay the message and amplify the response 1. Cyclic AMP (cAMP) is common second messenger 2. Lead to protein synthesis, metabolic activities, or cell division 3. Calcium ions (Ca²⁺): Act as second messengers in pathways, particularly in muscle contraction and neurotransmitter release. 3. Response: a. Response: The final molecule in the signaling pathway converts the signal to a response that will alter a cellular response b. Type of cells can respond differently to the same signals c. Example: i. Protein that can alter membrane permeability ii. Enzyme that will change a metabolic process iii. Protein that turns genes on or off 4. Important receptors: hydrophilic a. Concepts: i. Two broad groups of signaling molecules: hydrophilic and hydrophobic ii. Hydrophilic can’t pass through the cell membrane 1. Bind to ligand binding domain of extracellular receptor 2. Intracellular domain performed the response b. Hydrophilic receptors: -> c. GPCRs: G protein coupled receptors i. Largest category of cell surface receptors ii. Important in animal sensory systems iii. G protein: can bind to GTP and GDP, which is an energy molecule similar to ATP 1. Three parts with 2 anchored to the membrane. iv. Structural: 1. Spans across the membrane 7 times (alpha helices) v. vi. Step 1: Ligand binding causes cytoplasmic side to change shape 1. Allow for the G protein to bind to GPCR 2. Activates the GPR and G protein 3. In Alpha subunit: GDP becomes GTP 4. Alpha subunit dissociate with moves away from beta and gamma subunits vii. Step 2: Alpha subunit dissociate and regulate target protein 1. Activates a large amount of secondary messenger when target protein is activated (intermediate signaling molecules that amplifies the response inside the cell) 2. Parts of the activated G protein can then bind to the enzyme: a. Activates enzyme b. Amplifies signal and leads to a cellular response viii. Step 3: GTP hydrolyzed and becomes GDP 1. Everything go backs to normal ix. Example: epinephrine 1. Binds to epinephrine specific GPCR 2. GPCR activated 3. Swap out alpha subunit’s GDP for GTP 4. Alpha subunit will leave and attach to adenylate cyclase a. Take ATP and produce cAMP (second messenger) 5. cAMP will tell the cell to perform another function by amplifying the signal 6. Energy coming from the break down of glycogen to glucose x. d. Ligand Gated Ion channels: i. Located: in the plasma membrane ii. Important in the nervous system iii. Receptors that act as a gate for ions: 1. When a ligand binds to the receptor, the “gate” opens of closes allowing the diffusion of specific ions a. Vert specific shape and can only bind to some ligand b. Initiates a series of events that led to cellular response 2. Eg. Sodium potassium pump (3 NA+ in and 2 K out) e. Receptor protein kinases: i. Important in growth factors 1. Can cause problems in growth and differentiation of cells ii. Two in one protein: 1. Both a signal binding extracellular domain and kinase intracellular domain iii. Binding of signals to ligand binding protein of kinase will activate kinase domain iv. Transfers a phosphate group from ATP to protein, changing the shape of the protein to achieve a response v. Example: Receptor Tyrosine Kinase 1. Two receptor tyrosine kinase come together to receive the signal a. Cross linked dimer: a molecule made up of two protomers that are chemically joined by a covalent bond b. Activate tyrosine of the other receptor – cross phosphorylation 2. ATP converted to ADP to phosphorylate the other RPK 3. Different proteins come by and attach to phosphorylated tyrosine vi. 5. Important receptor molecules: hydrophobic a. Internal receptor proteins b. Cause changes in gene expression c. Eg. Hormones Changes in Signal transduction pathway: 1. Agonist: any ligand that binds to a receptor and causes a response a. Eg. Albuterol is an agonist of adrenaline receptors that cause airway to widen b. Structure similar to adrenaline 2. Antagonist: any ligand that binds to a receptor and initiates a response a. Binds to receptor protein but doesn’t activate it b. Eg. Caffeine: bind to adenosine receptor and prevents drowsiness c. Adenosine and caffeine have similar two ring structure 3. Endogenous ligand: normally occurring molecule that binds to receptors 4. Exogenous ligand: bind to receptor more tightly; triggering a response for a longer period of time 5. Mutation: a. Mutation in gene that encodes for receptor protein can result in changes of shape of the receptor so that it will no longer bind to its specific ligand b. Competitive inhibiter c. Other factors might tamper with the cell’s ability to produce secondary messengers – affect a number of subsequent steps d. Leptin: regulate appetite by reflecting amounts of fat cells in the body i. Mutation in leptin cell led to lack of leptin increased appetite e. Testosterone: male development in embryos i. Androgen receptors (receptor of testosterone) have mutation and prevent binding of testosterone ii. Develop female characteristics instead Feedback: 1. The body must be able to monitor its internal condition at all times: a. Set points: values for various physiological conditions that the body tries to maintain i. Has a normal range for which it can fluctuate (eg. Body temperature’s set point If 98.6 Fahrenheit. Normal range: 97-to-99-degree Fahrenheit b. Homeostasis: the state of relatively stable internal conditions i. Organisms detect and response to a stimulus ii. Balance, but dynamic iii. Through nervous and endocrine system (hormones) iv. The body maintains homeostasis through feedback loops 2. Feedback loops: a. Stimulus: a variable that will cause a response b. Receptor/sensor: sensory organs that detect a stimulus. This information is sent to the brain c. Effector: muscle or gland that will response d. Response: Changes (decrease or increase) the effect of the stimulus 3. Negative feedback: a. The most common feedback mechanism b. This type of feedback reduces the effect of the stimulus c. Eg. Sweat (thermoregulation), blood sugar (insulin), breathing rate 4. Positive feedback: a. This type of feedback increases the effect of a stimulus b. Continue until the snowball effect cause something to “break” in the system c. Eg. Child birth (oxytocin bind to receptors in uterus and it respond by contracting more, blood clothing, fruit ripening (caused by ethylene) 5. Homeostatic imbalances: a. b. c. d. Genetic disorder Drug or alcohol abuse Intolerable conditions (extreme heat or cold) Disease: when the body is unable to maintain homeostasis i. Eg. Cancer: the body can’t regulate cell growth ii. Eg. Diabetes: the body cannot regulate blood glucose levels 1. Type I: body doesn’t produce insulin 2. Type II: cells can’t respond to insulin e. Positive Feedback in Specific Scenarios i. In childbirth, oxytocin is released, increasing uterine contractions in a positive feedback loop that intensifies until birth. f. Feedback Loop Failures and Disease: i. Hyperglycemia in Diabetes: When insulin feedback fails, glucose levels remain high. Chronic hyperglycemia can damage tissues and organs over time. 6. Cell signaling as a mean of homeostasis a. In order to maintain homeostasis, the cells in a multicellular organisms must be able to communicate b. Communication occurs through a signal transduction pathway Cell cycle (prokaryotes): 1. Binary fission: a. 1.prokayote grown large enough to begin cell division b. 2.cell copies, replicates its DNA so that each daughter cell receives one copy c. 3.circular DNA attach to proteins on the inside of the cell membrane. After copied, there are two DNA molecules, each attached to the cell membrane at different sites d. 4.two attachment sites are initially close together. However, as growth continue, they break apart e. 5.when the cell is about twice its original size, new cell membrane and cell wall are synthesized at midpoint/constriction site f. 6.two daughter cells form g. 2. Type of asexual reproduction 3. Sometimes less than 20min Cell cycle: 1. Cell division process is an integral part of life 2. Allow for the reproduction of cells, growth of cells, and tissue repair 3. Cell cycle: the life of a cell from its formation until it divides 4. Reason behind cell division: SA: V ratio is too low 5. Organization of DNA: a. Cels must organize and package their DNA before division b. Only genes on DNA can be used to produce proteins i. DNA that’s used to produce protein is euchromatin (doesn’t bind to histone) ii. DNA that binds to histone: heterochromatin c. DNA associate with and wraps around proteins known as histones to form nucleosomes i. Strings of nucleosomes form chromatin ii. When a cell is not actively dividing, chromatin is in a noncondensed form iii. After DNA replication, chromatin condenses to form a chromosome d. Since the DNA was replicated, each chromosome has a duplicated copy i. The copies joint together to form sister chromatids ii. Centromere: the region on each sister chromatid where they are mostly closely attached iii. Kinetochore: proteins attached to the centromere that link each sister chromatid to the mitotic spindle iv. e. Relationship: gene -> DNA -> nucleosome -> chromatin -> Chromosome f. Genome: i. Def: all of a cell’s genetic information ii. Prokaryote: singular circular DNA iii. Eukaryote: one or more linear chromosomes 1. Humans: 46 2. Chimps: 48 3. Elephants: 56 iv. Homologous chromosomes: two chromosomes (one from mom and one from dad) that are the same length, have the same centromere position, and carry genes controlling the same characteristics 6. Types of cells: a. Somatic: body cells i. Diploid (2n): two sets of chromosomes, one set form each parents ii. Divide by mitosis iii. Humans: 2n= 46 1. 23 from mom 2. 23 from dad b. Gametes: i. Reproductive cells (eggs/sperm) ii. Haploid (n): one set of chromosomes iii. Divide by meiosis iv. Humans: n = 23 7. The cell cycle process. a. Consisted of alternating phases of interphase and mitosis b. Motor protein: They are proteins that “walk” along the microtubules and actin filaments, and they carry cellular cargo. They use energy to move things, including chromosomes during cell division. c. G1 -> S -> G2 -> Mitosis -> Cytokinesis d. Interphase: i. The longest portion of the cell cycle (90%) ii. G1: first gap phase 1. The cell grows and carries out normal functions 2. Single chromosome with only 1 chromatid 3. Prepare for replication of DNA 4. Organelles (such as centrosomes) are duplicated iii. S: synthesis phase: 1. DNA replication and chromosome duplication occurs 2. Longest period 3. Produce sister chromatids held together by centromere 4. Number of chromosomes remain the same 5. Twice the amount of DNA iv. G2: Second gap phase: 1. Final growth and preparation for mitosis 2. Produce tubulin to use in microtubules 3. e. M phase: i. Mitosis: nucleus divides ii. Cytokinesis: cytoplasm divides iii. Produces 2 identical diploid daughter cells iv. Function: growth and repair 1. Return G2 phase cells to G1 phase cells v. Prophase: 1. Chromatin condenses 2. Nucleoli disappears 3. Nuclear membrane dissolve 4. Duplicated chromosomes appear as sister chromatids 5. Mitotic spindle (microtubules) begins to form 6. Centrosomes move away from each other vi. vii. viii. ix. x. 7. Prometaphase: 1. Nuclear envelope fragments 2. Microtubules enter the nuclear area and some attach to kinetochores (protein found in centromere between centromere and spindle fiber) Metaphase: 1. Centromere are at opposite poles 2. Chromosomes line up at the metaphase plate (also called equator) 3. Microtubules are attached to each kinetochore Anaphase: 1. Sister chromatids separate and move to opposite ends of the cell due to the microtubules shortening 2. Cell elongates 3. Each chromatid now has its own centromere: considered separate chromosomes Telophase and cytokinesis: 1. Two daughter nuclei form 2. Nucleoli reappear 3. Chromosomes become less condensed Cytokinesis: 1. Animal: a cleavage furrow appears due to contractile ring of actin filaments a. Cleavage furrow starts from the side and move towards the middle 2. Plant: a. Vesicles produced by the Golgi apparatus travel to the middle of the cell and form a cell plate b. Cell plate formation starts from center and moves Regulation of the Cell Cycle: 1. Throughout the cell cycle there are checkpoints a. Control points that regulate the cell cycle b. Cells receive stop/go signals 2. Stop/go signals: a. “go”: cell completes the whole cell cycle b. “stop”: cell enters a nondividing (quiescent) phase 3. G0: a. Some cells stay in G0 forever (muscle/nerve cells) b. Some cells can be called back into the cell cycle c. Absence of preparation for DNA synthesis d. Do not undergo apoptosis i. Resting state ii. Can lead to apoptosis e. Some cells in G0 can still perform function: liver cells in G0 can still carry out metabolism and detoxification i. Nerve cells and muscle cells are always in G0 phase 4. G1 Checkpoint: a. Most important checkpoint b. Checks for cell size, growth factors, and DNA damage c. Can be caused by environmental factors such as UV rays d. Interfering until DNA damage is repaired 5. G2 checkpoint: a. Checks for completion of DNA replication and DNA damage b. “Go”: cell proceeds to mitosis c. “stop”: cell cycle stops and the cell will attempt to repair damage i. If damage cannot be repaired the cell will undergo apoptosis 6. M (Spindle) checkpoint: a. Checks for microtubule attachment to chromosomes at the kinetochores at metaphase b. “Go”: cell proceeds to anaphase and completes mitosis c. “stop”: cell will pause mitosis to allow for spindles to finish attaching to chromosomes 7. Reason for mutation: guard cells in check points are fake a. Allow “go” signals even when they’re not supposed to 8. Internal cell cycle regulators: a. Regulation of the cell cycle involves an internal control system that consists of: i. Proteins know as cyclins 1. Concentrations of cyclins vary 2. Cyclin is synthesized and degraded at specific stages of the cell cycle ii. Enzymes known as cyclin-dependent kinase (CDKs) 1. Concentration remains constant through each phase of the cell cycle 2. Active only when its specific cyclin is present b. Each cyclin CDK complex has a specific regulatory effect i. Active CDK complexes phosphorylate target proteins, which help regulate key events in the cell cycle ii. (research types of cyclin and CDK) c. When mitosis is about to begin complex called mitosis promoting factor (MPF) is formed and it triggers mitosis 9. Types of cyclin: a. Cyclin D/G1 cyclin: transition from G1 to S phase; interact with transcription factors; initiate DNA repair; cellular metabolism i. Activate tumor suppressor gene b. Cyclin E/ G1,S cyclin: from quiescence to S phase; often overexpressed to lead to proliferation i. Starts DNA replication c. Cyclin A/S cyclin: ensures that DNA only replicates once; initiates the start of S phase i. Prepare for cell division d. Cyclin B/M cyclin: activating tumor suppressor the whole time; starts mitosis 10. Density dependent inhibition: a. When cells tissue becomes too crowded, they will stop dividing 11. Anchorage dependence: Somatic cells will also exhibit anchorage dependence (the ability of cells to survive and grow by attaching to a surface) 12. Genes: a. Proto-oncogenes: propel cell division at a specific rate i. Necessary for regulated and controlled cell growth ii. It mutated: oncogenes 1. Promote abnormally high rates of cell division 2. Cause tumor 3. Function in a dominant way: a mutation in a single allele will cause the cell to grow without control b. Tumor suppressor genes: code for proteins that detect mutations in cell that may cause tumor to develop i. Single mutation in a tumor suppressor gene allele occurs, the cell will still possess one remaining unmutated tumor suppressor allele that is functional ii. Without mutation: help cells identify if a cell is dividing in a rate that is too fast iii. Function in a recessive way External cell cycle regulators: c. Growth factors: hormones released by cells that stimulate cell growth i. Signal transduction pathway is initiated ii. CDKs are activated lending to progression through the cell cycle d. Contact (or density) inhibition: i. Cell surface receptors recognize contact with other cells 1. Initiates signal transduction pathway that stops the cell cycle in G1 phase e. Anchorage dependence: i. Cells rely on attachment to other cells or the extracellular matrix to divide 13. Cancer: a. Normal cells become cancerous through DNA mutations b. DNA mutations: changes the DNA i. Cancer cells on average have accumulated 60 or more mutations on genes that regulate cell growth c. When DNA is damaged by radiation: i. Protein kinase is activated and phosphorylate a protein called p53 ii. P53 helps cell get past G1 checkpoint – if not, these genes guides the production of proteins that blocks the cyclin and its CDK from forming, which are necessary for getting past G1 checkpoint iii. P53 mutation cause cancer cells to get past G1 and divide without control – no safeguard 14. d. Normal cell: i. Follow checkpoints ii. Divide on average 20-50 times in culture iii. Go through apoptosis when there are significant errors e. Cancer cells: i. Do not follow checkpoints ii. Divide infinitely when culture 1. Considered to be “immortal” iii. Evade apoptosis and continue dividing even with errors f. Uncontrollable growth of cancer cells can lead to a tumor i. A mass of tissue formed by abnormal cells ii. Benign tumor: cells are abnormal, but not considered to be cancerous 1. Cells remain at only the tumor site and are unable to spread elsewhere in the body iii. Malignant tumor: mass of cancerous cell that lose their anchorage dependency and can leave the tumor site 1. Metastasis: when cells separate from the tumor and spread elsewhere in the body g. Cancer prevention: i. No smoking (cigarettes, vape products) ii. Eat healthy and drink water iii. Protect your skin from the sun by using SPE iv. Go to get regular cancer screening v. Treatment: Many cancer treatments target rapidly dividing cells by disrupting the cell cycle, often during S phase (e.g., chemotherapy drugs like methotrexate, which prevents DNA replication) or mitosis (e.g., taxol, which inhibits microtubule function). Other disease: a. Aneuploidy: Errors in chromosome separation during cell division can result in cells with abnormal chromosome numbers (aneuploidy), leading to disorders such as Down syndrome.