4BBY1030 Cell Biology & Neuroscience Lecture 5 PDF

Institute of Psychology, Psychiatry and Neuroscience Dr Clemens Kiecker 4BBY1030 Cell Biology & Neuroscience Lecture 5 Neuroscience Education Cell adhesion and junctional complexes Chapter 1 Extracellular matrix (ECM) Dr Clemens Kiecker Topic title: Cell types and subcellular structures 2 Two types...

Institute of Psychology, Psychiatry and Neuroscience Dr Clemens Kiecker 4BBY1030 Cell Biology & Neuroscience Lecture 5 Neuroscience Education Cell adhesion and junctional complexes Chapter 1 Extracellular matrix (ECM) Dr Clemens Kiecker Topic title: Cell types and subcellular structures 2 Two types of extracellular matrix Basement membrane/basal lamina 2D sheet on which epithelial cells reside Epithelium (Cells are tightly packed, binding to each other) ` 10 µm Fibrillar matrix Mesenchyme Essential Cell Biology 3D matrix composed of various fibres, in which cells such as fibroblasts are buried (Cells are sparse) Cell Section of mouse embryo, Nagai et al. J Cell Biol 2000;150:14991506 Mori et al. 2008, J Exp Med. 205: 43-51 Dr Clemens Kiecker Topic title: Cell types and subcellular structures 3 Basement membrane/basal lamina Underlies epithelia and surrounds some nonepithelial cells Main components: Dr Clemens Kiecker Topic title: Cell types and subcellular structures Collagen IV Laminin Nidogen Perlecan 4 Fibrillar matrix Deposited and constantly re-modelled by embedded cells Main components: Dr Clemens Kiecker Collagen I Fibronectin Elastin Proteoglycans Topic title: Cell types and subcellular structures 5 Chapter 2 Cell adhesion and junctions Dr Clemens Kiecker Topic title: Cell types and subcellular structures 6 Types of junctional complexes A. Tight junction B. Adherens junction C. Desmosome D. Gap junction E. Focal adhesion Dr Clemens Kiecker ` F. Hemidesmosome Topic title: Cell types and subcellular structures 7 Desmosomes and hemidesomosomes in the electron microscope 1. Pairs of dark, disk/button-like structures at cell-cell contacts= Desmosomes desmoGreek desmos "bond” “fastening” “chain” Cell 1 Cell 2 -some Greek sôma ”body” Cell 1 Cell 2 http://www.columbia.edu/itc/hs/medical/sbpm_histology_old/lab/lab11_micrograph.html Garrod et al. J Cell Sci. 2005 118:5743-54 2. Something looking like ‘half-desmosomes’ at cell-ECM interface= Hemidesmosomes Cell hemiGreek hēmi”half” ECM Borradori and Sonnenberg. J Invest Dermatol. 1999 112:411-8 Bars, 100 nm Dr Clemens Kiecker Topic title: Cell types and subcellular structures https://www.dictionary.com 8 (Hemi)desomosomes are linked to intermediate filaments Desmosome Dr Clemens Kiecker Hemidesmosome Topic title: Cell types and subcellular structures 9 The approximate scale of these structures A cell ~20 µm wide A desmosome ~500 nm high A hemidesmosome ~100 nm wide Array of hemidesmosomes at cell bottom Dr Clemens Kiecker Topic title: Cell types and subcellular structures 10 Intermediate filaments provide support against mechanical stress Epidermolysis bullosa (mutations in IF or desmosomal factors) Kasperkiewicz et al. 2017, Nat Rev Dis Primers. 3:17026 Has C and Bruckner-Tuderman L. Annu Rev Genomics Hum Genet. 2014;15:245-68. Dr Clemens Kiecker Pemphigus (autoantibodies against desmosomes) Topic title: Cell types and subcellular structures 11 Types of junctional complexes A. Tight junction B. Adherens junction C. Desmosome D. Gap junction E. Focal adhesion Dr Clemens Kiecker ` F. Hemidesmosome Topic title: Cell types and subcellular structures 12 Tight junctions surround the apical surface of epitelial cells Molecular Biology of the Cell Dr Clemens Kiecker Topic title: Cell types and subcellular structures 13 Tight junctions turn epithelia into barriers Control Claudin (TJ factor) knockout Furuse et al. 2002, J Cell Biol. 156:1099-111 Injection of purple dye under skin à spreads into upper layers in the Claudin knockout mouse Dr Clemens Kiecker Topic title: Cell types and subcellular structures Claudin knockout pups lose weight due to evaporation of water through skin 14 Gap junctions couple cells via permeable pores Dispersed in lateral membrane Apical TJ Lateral GJs Basal Gap junctions form ‘fenestrations’ (pores) that allow small molecules and ions to pass between cells à chemical and electrical coupling Dr Clemens Kiecker Topic title: Cell types and subcellular structures 15 Types of junctional complexes A. Tight junction B. Adherens junction C. Desmosome D. Gap junction E. Focal adhesion Dr Clemens Kiecker ` F. Hemidesmosome Topic title: Cell types and subcellular structures 16 Adherens junctions are linked to the actin cytoskeleton ‘Double headband’ Apical TJ AJ Basal Pollard et al. ‘Cell Biology’ 2e - Elsevier Actin-myosin can mediate contractile forces à bending of epithelia Dr Clemens Kiecker Topic title: Cell types and subcellular structures 17 Focal adhesions link the actin cytoskeleton to the ECM via integrins Focal adhesion protein F-actin Kanchanawong et al. Nature 2010;468:580-584 (Penny Morton) Molecular Biology of the Cell Basal lamina E. Focal adhesion Dr Clemens Kiecker Topic title: Cell types and subcellular structures F. Hemidesmosome 18 Focal adhesions form transiently during cell movement Focal adhesion dynamics in a migrating human cell - YouTube Focal Adhesions Actin Filaments https://cellix.imba.oeaw.ac.at/cytoskeleton/actin Dr Clemens Kiecker Topic title: Cell types and subcellular structures 19 Discovery of the first cell adhesion molecule Kyoto University, Japan Carnegie Institution, Baltimore, US (Photo taken in 1969) EDTA à sequesters Ca2+ Masatoshi Takeichi: reinvestigated dissociation ofamphibian embryonics (Johannes Holtfreter) Dr Clemens Kiecker Topic title: Cell types and subcellular structures 20 Cadherins are Ca2+-dependent adhesion molecules Dr Clemens Kiecker Topic title: Cell types and subcellular structures 21 Other types of junctions not covered today A. Tight junction B. Adherens junction Selectin-based adhesion of white blood cells in vessels (‘leukocyte rolling’) Neuronal synapse C. Desmosome Plasmodesma (= plant gap junction) D. Gap junction Septate junctions (= tight junctions in invertebrates) etc. etc. E. Focal adhesion ` Dr Clemens Kiecker F. Hemidesmosome Topic title: Cell types and subcellular structures 22 Cancer metastasis is intricately linked to cell adhesion Dr Clemens Kiecker Topic title: Cell types and subcellular structures 23 Thank you for your attention [email protected] © King’s College London. All rights reserved