Cell Signaling I Lecture Notes PDF

Cell signaling I Learning objectives: Understand the concept of signal transduction Understand the four major signaling systems: endocrine, paracrine, neuronal and contact-dependent Understand that lateral inhibition is mediated by contact-dependent Delta- Notch signaling Under...

Cell signaling I Learning objectives: Understand the concept of signal transduction Understand the four major signaling systems: endocrine, paracrine, neuronal and contact-dependent Understand that lateral inhibition is mediated by contact-dependent Delta- Notch signaling Understand the concept of nuclear hormone receptors acting as intracellular receptors Understand that cell surface receptors act via intracellular Neutrophil responding to molecules to elicit cellular chemotactic factors responses Understand the concept and the major types of molecular switches & their roles in  Prelim 3: Next Monday, Nov 11th All exam are taken on CANVAS: CANVAS/EXAM/Exam Instruction Check your new seat assignment (by Friday night Nov 8th ): either in Cal Auditorium or Klarman G70. Material: lectures 14-18 and sections 8-9; ***Note: we grade based on material taught in class Practice Prelim 3: CANVAS/EXAM TAs review sessions: Saturday/Sunday 1-4PM Biotech Racker Room (Instructions in CANVAS/EXAM) Instructor Office Hours: Wed 1:30-2:30pm Biotech 258 Thursday 7-8pm on zoom Full instructions on Canvas/Exams/Exam Instructions: It is your responsibility to read and follow the instructors. Not following the instructions can be considered cheating and may result in 0 in the Prelim and in further penalties. Use of “AI” app & “Grammerly” app during Canvas exam violates Cornell academic integrity and will result in 0 in the exam. (I suggest de-installing)  Gene Expression II Wrap-up Mechanisms Generating of Maintaining specialized transcription cell identity cell types regulation How do cells remember their developmental decisions and maintain cell type identity over time and through cell division? Positive feedback loops Histone modifications DNA methylation  Cell memory via positive feedback loops protein A activates transcription of itself (positive feedback) other genes that control cell fate Figure 8-22 ECB5  Cell memory via histone modifications Histone modification patterns can be passed on to daughter cells by the action of histone modifying enzymes Figure 5-25 ECB5  Cell memory via DNA methylation DNA methylation patterns can be passed on to daughter cells by the action of maintenance methyltransferase Figure 5-24 ECB5  Epigenetic inheritance Both histone modification and DNA methylation affect chromatin structure and patterns of gene expression without changing the nucleotide sequence. Epigenetic inheritance: patterns of gene expression are transmitted from parent to daughter cells without altering the actual nucleotide sequence of the DNA  Dosage compensation A mechanism to equalize the amount of X chromosome gene expression for males and females (i.e. XX and XY individuals have equal levels of expression of X-linked genes). Dosage compensation in mammals is via random inactivation of one of the X chromosomes in females. (Females are mosaics) X inactivation is irreversible and via an epigenetic mechanism. Rainbow (left) and her clone CC (right) A sex-linked color locus (C) has two alleles, O and B, for Orange and Black. Where an X chromosome bearing the O allele is inactivated, the melanocytes are black; where B is inactivated, the melanocytes are orange. Figure 5-28 ECB5  Cell signaling I: migration in response to signal Neutrophil responding to chemotactic factors  >7,000 of ~21,000 protein-coding genes in hum are devoted to cell signaling  General principle of cell signaling cell surface intracellular receptor intracellular signal relay amplify Extracellular signaling integrate Molecule (Ligand) distribute may alter: effector gene expression metabolism cytoskeleton etc Cell division Growth, Survival response: Migration Secretion, Figure 16-2 ECB5 Contraction, Differentiatio n The process of translating an extracellular signal into intracellular effectors that alter cell behavior = Signal Do not memorize! Signal Molecule Site of Origin Chemical nature Some Action Hormones Epinephrine (adrenaline) adrenal gland derivative of the amino acid tyrosine increases blood pressure, heart rate, and metabolism Cortisol adrenal gland Steroid (derivative of cholesterol) affects metabolism of proteins, carbohydrates, and lipids in most tissues Estradiol ovary Steroid (derivative of cholesterol) induces and maintains secondary female sexual characteristics Insulin β cells of pancreas protein stimulates glucose uptake, protein synthesis,and lipid synthesis in various cell types Testosterone testis steroid (derivative of cholesterol) induces and maintains secondary male sexual characteristics Thyroid hormone (thyroxine) thyroid gland derivative of the amino stimulates metabolism in many cell types acid tyrosine Local Mediators Epidermal growth factor various cells protein stimulates epidermal and many other cell types to proliferate (EGF) Platelet-derived growth factor (PDGF) various cells, including blood platelets protein stimulates many cell types to proliferate Nerve growth factor (NGF) various innervated tissues protein promotes survival and axonal growth of certain classes of neurons Histamine mast cells derivative of the amino acid histidine causes blood vessels to dilate and become leaky, helping to cause inflammation Nitric oxide (NO) nerve cells; endothelial dissolved gas causes smooth muscle cells to relax; regulates cells lining blood vessels nerve-cell activity Neurotransmitters Acetylcholine nerve terminals derivative of choline excitatory neurotransmitter at many nerve–muscle synapses and in central nervous system γ-Aminobutyric acid (GABA) nerve terminals derivative of the amino inhibitory neurotransmitter in central nervous system acid glutamic acid Contact-dependent Signal Molecules Delta prospective neurons; various other developing cell types Transmembrane protein inhibits neighboring cells from becoming specialized in same way as the signaling cell Essential Cell Biology, Fifth Edition Copyright © 2019 W. W. Norton & Company  Signals can act over a long or short (ex. Insulin) range (ex. Shh) Short range AUTOCRINE Long range The axon of a neuron can be far away from the neuronal cell body. The axon terminates at specialized junctions called synapses. Once activated, the neuron sends electrical impulses along the axon, leading to the release of Figure 16-3 Essential Cell Biology 4e  Signals can act over a long or short range AUTOCRINE Short range Long range Figure 16-3 Essential Cell Biology 4e Delta/Notch: an example of cell-cell contact signaling An example: Cell-cell signaling mediated by membrane bound ligand (Delta) and membrane Delta/Notch can mediate either: -inductive signaling bound receptor -lateral inhibition (Notch). more in Section 9  Delta/Notch: a classical example of Cell A lateral Cell B Identical cellsinhibition B compete for a X=Delta cell fate (e.g. bristle or neuron) A B A Section 9: (inductive signalin Cell A wins and adopts the fate by Delta/Notch The same signal can bind same or different receptors and induce different responses in different target cells same receptor different receptor Information conveyed by the signal depends on how the target cells receives and interprets the signal (their  Signals can act rapidly or slowly Figure 16-7 Essential Cell Biology 5e  Signals Summary Signals can be of different types Small or large molecules, light, mechanosensation, etc Signals can act over a long or short range Endocrine, paracrine (autocrine), synaptic, contact-dependent The same signal can induce different responses  General principles of signaling ignaling cell(s) Receptor Intracellular Signaling signaling pathwa molecule (Ligand) Effector(s) Target cell Response Modified from Figure 16-2 Essential Cell Biology 4e  Receptors can be intracellular or on the cell surface L19 Signaling II Figure 16-8 Essential Cell Biology 4e  Steroid hormones regulate transcription Nuclea r hormo ne recept or Each hormone binds a different receptor Each receptor acts at different sites in mall, hydrophobic molecules DNA A given hormone usually regulates Figure 16-10 Essential Cell Biology 4e  General principles of signaling ignaling cell(s) Receptor Intracellular Signaling signaling pathwa molecule (Ligand) Effector(s) Target cell Response Modified from Figure 16-2 Essential Cell Biology 4e  Functions of the intracellular signaling pathways adaptors adaptors kinases Intracellular phosphatases 2nd messenger’: GTP-binding proteins Signaling proteases Molecules other enzymes lipids (PIP2) 2nd messengers cGMP cAMP Ca++ Effectors Response Figure 16-9 Essential Cell Biology 5e  Many key intracellular signaling proteins act as molecular switches Kinases: Small GTPases: serine/threonine kinases Ras, Ran, Rab etc tyrosine kinases Figure 16-11 Essential Cell Biology 5e  Feedback regulation within an intracellular signaling pathway can adjust the cell’s response to a signal All-or- none respons e Response s that oscillate on and off Figure 16-14 Essential Cell Biology 4e Functions of the intracellular signaling pathways adaptors Intracellular Signaling Molecules Effectors Response Figure 16-9 Essential Cell Biology 5e  Integration of signals Integrates signals Figure 16-43 ECB5  Animal cells integrate and distribute multiple signals to produce diverse response Apoptosis = programmed cell death Figure 16-6 ECB5