Cell Junctions and Signalling (BIOL111 Lecture)

Cell Junctions Plants Communicating junctions Connecting junctions Animals + tunnelling nanotubes 3. Junctions in animal cells...

Cell Junctions Plants Communicating junctions Connecting junctions Animals + tunnelling nanotubes 3. Junctions in animal cells Connecting junctions Communicating junctions + tunnelling nanotubes  3. Connecting junctions in animal cells: tight junctions Tight junctions form a continuous seal, to prevent movement of liquids and material between cells Specific proteins hold cells together forming a “water-proof” layer. Alberts et al (2004) Molecular Biology of the Cell 4th ed. Figs 19.05  Tight Junctions Function Gut epithelium Important in epithelial tissues Tight junctions demonstrated using tracer molecules in the gut. Alberts et al (2004) Molecular Biology of the Cell 4th ed. Figs 19.03  Tight junctions also help form the blood:brain barrier The blood:brain barrier prevents molecules from passing from the blood into the central nervous system Tight junctions help to block passage of molecules between cells Tight junctions also help form the blood:brain barrier Neisseria meningitidis Tight junctions Coureuil M, et al. Mechanism of meningeal invasion by Neisseria meningitidis. Virulence. 2012 Mar 1; 3(2): 164–172. doi: 10.4161/viru.18639  Connecting junction 2: Adherens junctions Found in most tissue types In ~15% of breast cancer, cadherin function is lost Cadherins Plasma membranes Actin microfilaments  4. Communicating junctions in animal cells Gap junctions Pores that connect cytoplasm of adjacent cells Similar in function to plasmodesmata Found in most animal tissues  Structure of Gap Junctions formed by the protein connexin 6 connexin proteins form a pore pores from adjacent cells align to make the gap junction.  Function of Gap Junctions channel is 1.4 nm in diameter allow exchange of solutes below 1.2 kDa: ions, sugars, amino acids, and other small molecules opening regulated by Ca2+ and hormones functions in coordinating activities of cells within a tissue eg. muscle contractions  Where found Structure Communicating Function or connecting Gap Junctions Animals 1.5 nm pore Communicating Stable connections Most tissues 6 connexin proteins lined Exchange of solutes below 1.2 kDa: ions, sugars, up in the membrane of amino acids, and other small molecules between cells both cells Coordinate activities of tissues eg. Muscle contractions Tunneling nanotubes Plasmodesmata Tight Junctions Adherens Junctions  Cell junctions key points Multicellular organisms use junctions between cells for communication and connection Plant cells communicate through plasmodesmata Animal cells connect to each other using tight junctions and adherens junctions Animal cells communicate through gap junctions and tunnelling nanotubes  Biol111: Cellular Biology and Biochemistry Lecture 33 Cell Signalling Pathways Today’s Outline 1. Overview of cellular signalling 2. Different types of cellular signalling 3. Different types of receptors available to a cell (reception) Two receptors that are on the cell surface, how they respond to signals One receptor on the inside of the cell, and how it responds to signals Thursday’s Outline (ish) 4. How these signals are transferred (transduction) from the plasma membrane to inside the cell through the use of second messengers 5. How signals can be amplified (phosphorylation cascades) 6. How the cell reacts to these signals (response) 7. How cells are specific in what signals they respond to  1. Introduction to signalling: Sensing What senses do we, as humans, have? Sight Sound Taste Smell Touch  Sensing: detection of a signal Can have a signal, but can you detect it? UV light is all around us, but we don’t see it. Must have a detection system. humans don’t detect electrical or magnetic signals. humans don’t detect ultrasound, UV Must be able to process and respond to the signal. bats can take an echo and generate spatial information. birds can sense a magnetic signal and navigate accordingly plants can sense gravity and grow directionally  What can cells sense? Multicellular organisms sense signals (light, touch, sound etc) using specialised organs Cells also sense signals, but using proteins called receptors What can cells sense? Sight Temperature Sound Taste Smell Touch  An Overview of Cellular Signalling Signalling allows responses to external change in: unicellular organisms multicellular organisms (animals, plants, fungi) cells within multicellular organisms Signalling enables co-ordination in multicellular organisms. Signalling at a cellular level involves 3 processes: 1 signal reception 2 signal transduction 3 signal response Signal reception - Signal transduction - Signal response  Cellular signalling Sometimes the cell that detects the signal is the same as the one that responds 1. Signal: a nutrient 1. Signal: a toxin is is detected by a detected by a receptor receptor 2. Signal is relayed 2. Signal is relayed (transduced) (transduced) through the through the cytoplasm to the cytoplasm to the flagella motor flagella motor 3. Response: 3. Response: keep swimming stop swimming in that direction in that direction  Cellular signalling Sometimes the cell that detects the signal is a long way away from the ones that respond Signal (heat) is Signal is relayed detected by (transduced) as thermoreceptors an electrical in the skin signal through the spine Muscles respond mechanically to the signal by contracting  2. Kinds of cellular signalling 1. Direct cell-to-cell signalling 1A. Cell junctions 1B. Cell-cell recognition  2. Kinds of signalling 2. Local signalling 2A. Paracrine signalling 2B. Synaptic signalling  2. Kinds of signalling 3. Long-distance signalling Called endocrine signalling Mediated by hormones  2. Kinds of signalling 3. Long-distance signalling Called endocrine signalling Mediated by hormones  2. Kinds of signalling Signalling molecules can be Gaseous, water-soluble, lipid-soluble Small molecules or proteins Ethylene, gas Estrogen, lipid-soluble Insulin, a protein Reception - Transduction - Response * signal reception * signal transduction * signal response = change in protein activity or expression. Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.06  3. Reception of signals A signalling molecule binds to a receptor and it changes shape. Receptors are specific for certain signals So that only the correct cells respond “lock and key” So that the cells don’t respond to the wrong signals A ligand is the specific signalling molecule that binds to a specific receptor receptor ligand Signal reception - Signal transduction - Signal response  3. Reception of signals Receptors: Cell-surface receptors: i. Ligand-gated ion channel receptors. ii. G protein-coupled receptors. iii. Enzyme-coupled receptors Cytoplasmic receptors: iv. Steroid receptors 30% of human proteins are cell surface receptors! Signal reception - Signal transduction - Signal response Ligand-Gated Ion Channel Receptors System involves: * signal molecule (wide range possible). * gated ion channel. When the signalling molecule binds to the channel, it opens and allows the flow of specific ions. It is critical that the gate returns to the closed position at the end of the signal. Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.07 Ligand-Gated Ion Channel Receptors Example: chemical synapses Ligand: neurotransmitter eg. Dopamine, acetyl choline Receptor: Transmitter-gated ion channel Effect: activation of the next nerve cell by ions entering the cell Alberts et al. (2014) Molecular Biology of the Cell, Fig. 11.36  II. G Protein-Coupled Receptors (GPCRs) G protein receptors are signal receptors found associated with the plasma membrane. Found in all eukaryotes. 800 different GPCRs in humans 60% of drugs target GPCR pathways Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.07  G Protein-Coupled Receptors System involves: signal molecule (ligand) G protein-coupled receptor G protein enzyme. Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.07  II. G Protein-Coupled Receptors (GPCRs) G proteins are GTP-binding proteins Inactive G-protein  ATP  GTP Active G-protein  GDP Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.07  G Protein-Coupled Receptors System involves: The signal molecule binds to the signal molecule (ligand) receptor. G protein-coupled receptor Receptor shape changes to allow G protein G-protein to bind enzyme. G protein is activated by switching GDP for GTP 1. Resting state 2. GPCR activates G-protein Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.07  G Protein-Coupled Receptors Activated G-protein then G protein deactivated by activates an enzyme that hydrolysis of GTP to GDP. triggers a cellular response Signalling system turned off and reset. 3. G-protein activates enzyme 4. System returns to resting state Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.07  G Protein-Coupled Receptors Examples: Adrenaline receptor Rhodopsin: photoreceptor Reece et al. (2011) Campbell Biology, 9th ed, Fig. 11.07  Today’s Key Messages Cells can detect and respond to a wide variety of signals, most of which are chemical signals Signalling can be direct, local, or long-distance Signalling molecules are diverse in structure and solubility Signalling consists of three steps Signal reception Signal transduction Signal response Ligand-ion channels and GPCRs are examples of membrane- bound receptors