BES 107 Introduction to Cell Biology Part 5 - Cell Signalling (Winter 2025) PDF

BES 107 Introduction to Cell Biology Part 5 – CELL SIGNALLING Campbell’s Biology Chapter 11 Winter 2025 Sophon Bailey All figures are from Campbell’s Biology, © 2021 Pearson Press, unless otherwise attributed....

BES 107 Introduction to Cell Biology Part 5 – CELL SIGNALLING Campbell’s Biology Chapter 11 Winter 2025 Sophon Bailey All figures are from Campbell’s Biology, © 2021 Pearson Press, unless otherwise attributed. Course content, digital or otherwise, created and/or used within the context of the course is to be used solely for personal study, and is not to be used or distributed for any other purpose without prior written consent from the content author(s). LEARNING OBJECTIVES Understand the need for chemical signalling in all cells Distinguish the different distances of chemical signalling inmulticellular eukaryotes Apply the 3 stages of signalling to understand common signalling mechanisms (e.g. epinephrine) Differentiate the 3 types of cell surface receptors and their mechanism of transduction Understand how different cellular responses are generated in the nucleus or cytoplasm Recognize the ways responses are regulated and varied in different cell types 2 BACTERIAL SIGNALLING Multi-cellular organisms use cell communication to coordinate tissue functions Single celled organisms use simple communication to coordinate behaviours in a population All bacterial cells secrete signalling factors The level of factors indicates the population density  quorum sensing Quorum sensing can trigger sporulation when population density is too high Myxobacteria sporulating in response 3 to low nutrient availability Campbell’s Biology © 2021 Pearson Press EUKARYOTIC SIGNALLING Multi-cellular organisms use several different types of chemical signalling Juxtacrine –immediately adjacent cells (contact or chemical signalling) Paracrine –short-distance local chemical signalling › Autocrine –self-signalling with chemical messengers Endocrine –long-distance signalling through circulation (hormones) 4  JUXTACRINE SIGNALS Gap junctions (animals) and plasmodesmata (plants) connect the cytoplasm of adjacent cells Cell junctions allow free exchange of signalling molecules and ions Cell surface antigens and receptors allow communication by contact –important in immune function 5 Campbell’s Biology © 2021 Pearson Press  PARACRINE SIGNALS Paracrine signals diffuse short distances to targets Chemical synapses in the nervous system are highly specialized paracrine sites Many paracrine signals are released from vesicles by exocytosis 6 Campbell’s Biology © 2021 Pearson Press  ENDOCRINE SIGNALS Endocrine signals coordinate functions between different tissues Hormones circulate through blood allowing distant tissues to respond in concert 7 Campbell’s Biology © 2021 Pearson Press Campbell’s Biology © 2021 Pearson Press 3 STAGES OF 1 –signal is received at a cell surface receptor 2–signal is transduced through an intracellular cascade SIGNALLING 3 –response to signal is generated within the cell 8  ‘FIGHT-OR-FLIGHT’ RESPONSE Stress triggers a coordinated physiological shift in the human body Epinephrine (adrenaline) is released from the adrenal glands in response to perceived threat Adrenergic signalling triggers a change of blood flow, metabolism, alertness, and focus to identify and escape threats › Blood flow shifts from internal organs to skeletal muscles › Metabolism shifts to mobilize stored glucose › Respiration (heart and breathing) increase › Anxiety increases alertness, perception, and motor control 9 Campbell’s Biology © 2021 Pearson Press  CELL SURFACE RECEPTORS Receptors are transmembrane proteins Extracellular domain has a binding site for a specific ligand molecule Intracellular domain has a mechanism for transducing the signal Campbell’s Biology © 2021 Pearson Press Adrenergic receptors are G-protein coupled receptors that respond to epinephrine and norepinephrine 10 CELL SURFACE RECEPTORS G-protein coupled receptors –transduce through a G-protein mechanism and chemical second messengers Kinase receptors –have an intracellular kinase to phosphorylate protein targets in the cell Ion channel receptors –allow ions to cross the membrane when ligands bind 11 Becker’s World of the Cell, 9e © 2016 Pearson Education Inc, Jeff Hardin and Gregory Bertoni  G-PROTEINS G proteins are a specialized GTPase enzyme that acts as a GDP-GTP switch toggle switch G-protein GDP-bound: inactive G-protein GTP-bound: active GDP GTP GTP hydrolysis Slowly hydrolyzes GTP to self-terminate Inactive –GDP bound Active –GTPbound Includes GPCR signalling and small GTPase in other signalling cascades 12 ADRENERGIC GPCR G-proteins come in different forms and second messengers › Gi –inhibits via ↓ cAMP › Gs –stimulates via ↑cAMP › G q –modulates via ↑ IP3 and Ca2+ Adrenergic receptors come in two forms with different G-protein coupling › α receptors –Gi coupled –found in visceral organs, reduces blood flow › β receptors –Gs coupled –found in skeletal muscles and lungs, increases blood flow and respiration 13 Campbell’s Biology © 2021 Pearson Press  Event Total SIGNAL s 1 1 AMPLIFICATION 10 10 The main effect of transduction is 10 102 amplifying a signal Each step occurs 10 103 multiple times Final response is 10 104 very large with only a small required 10 105 input 14 Campbell’s Biology © 2021 Pearson Press INTRACELLULAR RECEPTORS Certain hydrophobic signals do not require a cell surface receptor to signal across the cell membrane › Hydrophobic molecules can diffuse across lipid bilayers › Steroid hormones (androgens, estrogens, and glucocorticoids) › Lipid-based signalling molecules (prostaglandins, endocannabinoids) Hydrophobic signals bind intracellular receptors that can directly elicit a response without a signal transduction process 15 Campbell’s Biology © 2021 Pearson Press KEY POINTS Cell-cell communication is critical in all forms of cellular life (e.g. quorum sensing in prokaryotes, coordinating tissue functions in animals and plants) Eukaryotic cells use different molecules to signal short (juxtacrine, paracrine) or long (endocrine) distances Most signalling molecules require a cell surface receptor (transmembrane protein) to bind a specific ligand › Ion channel receptors, G-protein coupled receptors, kinase receptors › 1 –Reception; 2 –Transduction; 3 –Response Hydrophobic signalling molecules (steroid hormones and lipid modulators) can use an intracellular receptor to directly elicit a response in the cell 16 CELLULAR RESPONSES Signal pathways lead to regulation of one or more cellular activity –“output response” Nuclear response –change in protein quantity by altering gene expression › Pathway regulates a transcription factor Cytoplasmic response –change in enzyme activity › Ion flux through channels › Enzyme phosphorylation / dephosphorylation › Protein cleavage by proteases 17 Campbell’s Biology © 2021 Pearson Press  CYTOPLASMIC RESPONSE Enzyme regulation is a common cytoplasmic response Adrenergic signalling activates glycogen phosphorylase to release stored glucose for fight-or- flight responses 18 Campbell’s Biology © 2021 Pearson Press  REGULATION OF RESPONSE Different cells respond differently to the same stimulus › Different receptors for the same signal › Different signal path for the same receptor Many signalling pathways intersect or have cross-talk Signalling pathways are complex and interconnected 19 Campbell’s Biology © 2021 Pearson Press RESPONSE REGULATION Responses are affected by many factors: 1. Amplification of the signal 2. Specificity of the response » Different receptors or different coupling » Each cell expresses a different collection of proteins 3. Overall efficiency of response » Enhanced by scaffolding 4. Termination of the signal » Each step is transient and reversible Campbell’s Biology © 2021 Pearson Press KEY POINTS Output responses of signalling paths have two major effects › Nuclear responses engage transcription factors to modify gene expression  alter protein / enzyme levels › Cytoplasmic response drives regulation of enzyme activity › Nuclear responses tend to be more persistent, cytoplasmic responses tend to be more rapid and transient Signalling responses vary between different cells › Different receptors and different signal transduction pathways › High amounts of cross-talk between pathways 21