2016 H2 Topic K Cell Signalling

NANYANG JUNIOR COLLEGE H2 Biology Cell Signalling J2/2016 1 TOPIC K: CELL SIGNALLING Learning Outcome Candidates should be able to Core Topic 6 (o) Describe the three main stages of cell signalling – ligand-receptor interaction, signal transduction (inclusive of phosphorylation and signal amplification) and cellular responses. (Limited to an overview of insulin & RTK signalling and glucagon & G -protein signalling. Candidates will be expected to generalise their understanding of t hese systems in solving problems involving other cell signalling systems.) Advantages and significance of having a cell signalling system may be required. Content Outline 1. Introduction 2. Types of Cell Signalling (a) Local Signalling (b) Long Distance Signalling 3. Main Stages of Cell Signalling (a) Ligand-receptor interaction (i) Cell surface receptors  Ion channel receptor  G protein-coupled receptor  Receptor tyrosine kinase (ii) Intracellular receptor (b) Signal transduction (i) Phosphorylation cascade (ii) Second messengers (iii) Signal amplification (c) Cellular response 4. Advantages and Significance of a Cell Signalling System 5. Specific Examples of Cell Signalling Pathways (a) Glucagon-GPCR Signalling (b) Insulin-RTK Signalling (c) Generation of nerve impulses (d) Activation of cellular defence mechanism References 1. Campbell N. A. and Reece J. B. (2008). Biology. Chapter 11: Cell Communication. Eighth Edition. Benjamin Cummings Publishing, Inc. 2. Brooker R. J. et. al. (2008). Biology. Chapter 9: Cell Communication and the Regulation of the Cell Cycle. First E dition. McGraw-Hill Companies. 3. Alberts B. et. al. (1998). Essential Cell Biology – An Introduction to the Molecular Biology of the Cell. Chapter 15: Cell Communication. First Edition. Garland Publishing, Inc. 4. Karp G. (1996). Cell and Molecular Biology – Concepts and Experiments. Chapter 15: Cell Signalling: Communication between Cells and Their Environment. Second Edition. John Wiley and Sons, Inc.

NANYANG JUNIOR COLLEGE H2 Biology Cell Signalling J2/2016 2 1. Introduction The trillions of cells in a multi -cellular organism must communicate with each other to coordinate their activities. They do so by means of signal molecules, which include proteins, small peptides, amino acids, nucleotides, steroids, fatty acid derivatives and even dissolved gases such as nitric oxide. The cell signalling process helps ensure that c rucial activities occur in the correct cells, at the right time and in coordination with other cells in the organism. 2. Types of Cell Signalling Cells in multi-cellular organisms usually communicate via ligands / signal molecules (“first messengers”) targeted for cells that may be adjacent (local signalling) or may not be immediately adjacent (long distance signalling). (a) Local Signalling Direct contact between cells  Cell junctions In both plants and animals, cells may communicate via cell junctions, where cytoplasm of adjacent cells connect directly e.g. gap junction in animals and plasmodesmata in plants.  Cell-cell recognition In animals, cell may communicate between membrane bound molecules on the cell surface membrane. Communication by direct contact between cells

NANYANG JUNIOR COLLEGE H2 Biology Cell Signalling J2/2016 3 In other cases, signal molecules are secreted by the signalling cell, which travel short distances and influence cells in the vicinity  Paracrine signalling e.g. growth factor promote cell division and growth. Numerous cells can simultaneously receive and respond to the molecules of growth factor produced by a single cell in their vicinity.  Synaptic signalling e.g. neurotransmitters (such as acetylcholine) diffusing across synap ses between neurones. (b) Long Distance Signalling For long distance signalling, signal molecules known as hormones are secreted into the circulatory system (e.g. bloodstream of an animal or the sap of a plant) to act on distant target cells.  Specialised animal cells release hormone molecules (e.g. insulin and glucagon) into blood vessels of the circulatory system to other parts of the body, where they reach target cells that can recognise and respond to the hormones. This is known as endocrine signalling.  Plant hormones (e.g. auxin, a growth hormone) sometimes travel in vessels but more often reach their targets by moving through cells or by diffusion through the air as a gas. Local and long distance cell signalling

NANYANG JUNIOR COLLEGE H2 Biology Cell Signalling J2/2016 4 Experimental Evidence of Cell Signalling Earl W. Sutherland (from Vanderbilt University, won Nobel Prize 1971) investigated how animal hormone adrenaline stimulates the breakdown of the storage polysaccharide, glycogen, within liver and skeletal muscle cells. Glycogen breakdown releases the sugar glucose -1-phosphate, which the cell converts to glucose-6-phosphate. Glucose-6-phosphate can then be used by the cell (e.g. liver cell) for energy production. Alternatively, the compound can be stripped of phosphate and released from the liver cell into the blood as glucose, which can fuel cells throughout the body. Thus, one effect of adrenaline, which is secreted from the adrenal gland during times of physical or mental stress, is the mobilization of fuel reserves. Sutherland’s research team disco vered that adrenaline stimulates glycogen breakdown by activating glycogen phosphorylase (cytosolic enzyme) in intact cells. When adrenaline w as added to a test tube containing the enzyme glycogen phosphorylase and glycogen , no breakdown occurred. This implies that adrenaline does not interact directly with the enzyme responsible for glycogen breakdown and that the cell surface membrane is somehow involved in the transmission of the signal.

NANYANG JUNIOR COLLEGE H2 Biology Cell Signalling J2/2016 5 3. Main Stages of Cell Signalling For a cell to resp ond when it encounters a signal, the signal must first be recognis ed by a specific receptor molecule on the cell surface and then transmitted to the cell’s interior before an appropriate cellular response can occur. Cell signalling can be divided into three stages: (a) Ligand-receptor interaction (b) Signal transduction (c) Cellular Response Three main stages in cell signalling (a) Ligand-receptor interaction The ligand / signal molecule is complementary in shape to a binding site on the receptor and attaches itself there. There is specificity in the ligand-receptor binding. Binding of the ligand to the receptor activates the receptor. Generally, there are two types of ligands: (i) Molecules that are large and/or hydrophilic.  A large class of ligand molecules cannot pass through the cell surface membrane of the target cell.  Examples include insulin molecule and glucagon molecule.  The receptor proteins for these signa l molecules have to lie in the cell surface membrane of the target cell and relay the message across the membrane. (ii) Molecules that are small and hydrophobic.  A smaller, class of ligands consisting molecules that are able to diffuse across the cell surface membrane.  Examples include steroid hormones (like cortisol, estrogen and testosterone) and thyroid hormones.  The receptors for these signal molecules have to lie in the interior of the target cell and when bound to their ligands, they generally act as gene regulatory proteins.

NANYANG JUNIOR COLLEGE H2 Biology Cell Signalling J2/2016 6 Corresponding to the two classes of signal mo lecules, there ar e also two classes of receptors; cell surface receptors and intracellular receptors. (i) Cell surface receptors A cell surface receptor is usually a transmembrane protein embedded in the cell surface membrane of the target cell. It allows the cell to receive the