- 1 Introduction
- 2 Objectives
- 3 History
- 4 Why Adhesion?
- 5 Types of Junctions
- 6 Prokaryotes
- 7 Unicellular Eukaryotes
- 8 Multicellular Eukaryotes
- 9 Types of Adhesion
- 10 Adhesive Functions
- 11 Adhesion Characteristics
- 12 Types of Adhesion Molecules
- 13 Selectins
- 14 Integrins
- 15 Cell Junction Types
- 16 Junctions Overview - Typical Epithelia
- 17 Extracellular Matrix
- 18 Integrins
- 19 Abnormalities
- 20 References
- 21 Working Area
- 22 2015 Course Content
Lets stick together!
This lecture introduces the concept of cell adhesion. Unicellular organisms use to adhere to the environment, nutrition or pathogenesis. Multicellular organisms require adhesion for cells to adhere to each other and the extracellular matrix. Cell adhesion occurs through specific cellular specializations and molecules and has both static and dynamic functions. This topic will be revisited in lectures on extracellular matrix, cell cytoskeleton and signalling.
See also ANAT3231 Projects 2011 Junctions
- Broad understanding of cell adhesion with other cells and extracellular matrix
- Understanding of different adhesion proteins
- Understanding of different forms of adhesion junctions
- Understanding of biological role of adhesion
- Brief understanding of adhesion abnormalities
Below are some example historical research finding related to cell junctions from the JCB Archive.
1963 Defining junctional complexes A mess of nomenclature is sorted out by Marilyn Farquhar and George Palade, who use superb microscopy to define three of the four major types of cell–cell junctions in the polarized epithelial cells of vertebrates.
1967 Defining gap junctions Jean-Paul Revel and Morris Karnovsky unite the fields of adhesion and intercellular current transfer around a distinct, structural correlate called the gap junction.
1967 Endothelial tight junctions form the blood–brain barrier What is the cellular correlate of the so called blood-brain barrier? Thomas Reese and Morris Karnovsky find that it is the junctions between endothelial cells in the brain vasculature. Their discovery comes thanks to three factors: high resolution electron microscopy; the development of sensitive tracer methods; and a fortuitous lunch date.
1977 The sticky business of discovering cadherins A change in the recipe for a trypsin solution allows Masatoshi Takeichi to distinguish calcium-dependent adhesion.
1984 Sticking it out with tight junctions With persistence and a species change, tight junction proteins are isolated.
- Adhesion refers to “stickiness”
- Evolution of multicellular organisms developed specialized cells and tissues
- Embryonic development also allows differentiation of different cell/tissue types
- Interaction between cell-cell and cell-extracellular matrix by specific contacts
- Note the Cell Biology definition is different from the Clinical term
- Clinical term “adhesions” bands of scar-like tissue forming between two surfaces inside the body
Types of Junctions
- Prokaryotes adhesion molecules usually termed "adhesins"
- occur on pili (fimbriae), flagellae, or the cell surface
- adhesion first step in colonization
- express multiple adhesion molecules for nutrition, migration and pathogenesis
- malarial parasite (Plasmodium falciparum) uses circumsporozoite protein, an adhesion molecule, to bind to liver cells
- merozoite surface protein, to bind to red blood cells
- Maintains body form and structure
- Tissues organized during development
- Can be used for cell migration
- Cell signalling alteration in disease
Types of Adhesion
- Cell-extracellular matrix
- Basal lamina assemble and organize epithelia
- Smooth muscle
- Maintains integrity during contraction
- Binds growth factors
- Neurons growth cone guidance, fasiculation
- Cell Migration
- Development - migration, cell sorting, tissue development
- Transmigration, wound healing, macrophages
Except migrating cells and embryonic
Changes with development
Loose adhesion when mature or disease (Erythrocytes, cancer)
Types of Adhesion Molecules
Each type of junction involves specific adhesion molecules embedded in the cell plasma membrane.
- Immunoglobulin Superfamily
See additional information on interns below.
Cell Junction Types
The above adhesion molecules, along with other associated proteins and cytoskeleton elements, cluster on the plasma membrane to form identifiable cell junctions.
- Desmosomes (macula adherens)
- Adherens Junctions (zonula adherens)
- Septate Junctions
- Tight Junctions
- Gap Junctions
- Tunneling nanotubes
cell anchored to extracellular matrix
Present in tissues subject to shear or lateral stress
microfilaments anchor the plaque that occurs under the membrane of each cell
plaques not as dense also occur as hemiform
heart muscle, layers covering body organs, digestive tract
- Discovered by R.L. Wood 1959
- found in invertebrate tissues - adhesion, sealing, communication
- septa = walls, regularly spaced cross bars 15-17 nm
Electron Micrograph Filtered Image of Two Connexons
- Discovered by A. Rustom and H.-H. Gerdes in 2004
- allowing direct communication between cells
- connecting cells at a distance of up to several cell diameters
- tubes with a diameter of 50-200 nm
Junctions Overview - Typical Epithelia
- Tight Junction - seals neighbouring cells.
- Adherens Junction - joins actin bundles between cells.
- Desmosome - joins intermediate filaments between cells.
- Hemidesmosome - anchors cell intermediate filaments to ECM (basal lamina in epithelia, ECM CT)
- Gap Junction - cell-cell communication (signalling), passage of small molecules.
- Tunneling nanotubes - cell-cell communication, passage of organelles.
Mammals have genes for 18 alpha and eight beta integrins Role in cell adhesion to extracellular matrix (ECM) basement membranes Induction of cell polarization by adhesion Cell migration through ECM Mainly receptors for ECM proteins Fibronectin, laminin, collagen Some heterotypic binding Ig superfamily Interact with cell cytoskeleton signalling
Focal adhesion migrating cell
- Adhesion is closely coupled with the protrusions of the leading edge of the cell (filopodia and lamellipodia).
- Adhesions (nascent adhesions) initially form in the lamellipodium (although adhesions may also be associated with filopodia) and the rate of nascent adhesion assembly correlates with the rate of protrusion.
- Nascent adhesions either disassemble or elongate at the convergence of the lamellipodium and lamellum (the transition zone).
- Adhesion maturation to focal complexes and focal adhesions is accompanied by the bundling and cross-bridging of actin filaments, and actomyosin-induced contractility stabilizes adhesion formation and increases adhesion size.
Proteins linking integrins to actin cytoskeleton
- Talin - actin-binding protein that forms antiparallel homodimers. The amino-terminal FERM (protein 4.1, ezrin, radixin and moesin) domain binds β-integrin tails and is sufficient to activate integrins. The carboxy-terminal rod domain interacts with vinculin and filamentous actin.
- Vinculin - actin-binding protein associated with cell–cell and cell–extracellular matrix junctions. A globular head domain linked to a tail domain by a short Pro-rich sequence. The intramolecular interaction between the head and tail masks binding sites for talin, actin and other effectors.
- α-actinin - actin cross-linking protein of the spectrin superfamily. Forms antiparallel homodimers in a rod-like structure, with one actin-binding domain on each side of the rod. It can therefore cross link two filaments of actin.
- Kindlins - members of a family of conserved FERM domain–containing proteins named after the gene mutated in Kindler syndrome, a rare skin blistering disease. Not clear how kindlins activate integrins, they seem to act synergistically with talins to do so.
Integrin–ligand binding and clustering PMID 27872252
- pemphigus and bullous impetigo - antibodies made against one of their own desmosomal cadherin proteins
- antibodies bind to and disrupt the desmosomes that hold together skin epithelial cells
- severe skin blistering, leakage of body fluids
Arrhythmogenic right-ventricular cardiomyopathy (ARVC)
- not the cause but transformed cells loose adhesion, able to "break away" and spread (metastasis).
Essential Cell Biology
- Chapter 19 Tissues Epithelial sheets and Cell-Cell Junctions p606
Molecular Biology of the Cell
Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002
- Molecular Biology of the Cell 4th ed. - V. Cells in Their Social Context Chapter 19. Cell Junctions, Cell Adhesion, and the Extracellular Matrix
- Cell Junctions
Molecular Cell Biology
Lodish, Harvey; Berk, Arnold; Zipursky, S. Lawrence; Matsudaira, Paul; Baltimore, David; Darnell, James E. New York: W. H. Freeman & Co.; c1999
- Molecular Cell Biology - Chapter 22. Integrating Cells into Tissues 22.1. Cell-Cell Adhesion and Communication
- Cell-Cell Adhesion and Communication
- Cell-Matrix Adhesion
The Cell- A Molecular Approach
Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000
- The Cell - A Molecular Approach - III. Cell Structure and Function Chapter 12 The Cell Surface
- Cell-Cell Interactions
- Cell Adhesion Molecules
Search Online Textbooks
- "cell junctions" Molecular Biology of the Cell | Molecular Cell Biology | The Cell- A molecular Approach | Bookshelf
- PubMed is a service of the U.S. National Library of Medicine that includes over 18 million citations from MEDLINE and other life science journals for biomedical articles back to 1948. PubMed includes links to full text articles and other related resources. PubMed
- PubMed Central (PMC) is a free digital archive of biomedical and life sciences journal literature at the U.S. National Institutes of Health (NIH) in the National Library of Medicine (NLM) allowing all users free access to the material in PubMed Central. PMC
- Online Mendelian Inheritance in Man (OMIM) is a comprehensive compendium of human genes and genetic phenotypes. The full-text, referenced overviews in OMIM contain information on all known mendelian disorders and over 12,000 genes. OMIM
- Entrez is the integrated, text-based search and retrieval system used at NCBI for the major databases, including PubMed, Nucleotide and Protein Sequences, Protein Structures, Complete Genomes, Taxonomy, and others Entrez
- "cell junctions" PubMed reviews | PubMed all articles | PMC reviews | PMC all articles | OMIM | Entrez all databases
- Tight junctions/adherens junctions: basic structure and function. Niessen CM. J Invest Dermatol. 2007 Nov;127(11):2525-32. Review.. PMID: 17934504
- The tight junction: a multifunctional complex. Schneeberger EE, Lynch RD. Am J Physiol Cell Physiol. 2004 Jun;286(6):C1213-28. Review. PMID: 15151915 Am J Physiol Cell Physiol
- The desmosome and pemphigus. Waschke J. Histochem Cell Biol. 2008 Jul;130(1):21-54. Epub 2008 Apr 3. Review. PMID: 18386043
- Tunneling Nanotubes. Rustom A. Ann N Y Acad Sci. 2009 Oct;1178:126-39. Review. PMID: 19845633
There is also a gallery of all images added sorted by date New Images (the search option will only search by image file name).
2015 Course Content
Lectures: Cell Biology Introduction | Cells Eukaryotes and Prokaryotes | Cell Membranes and Compartments | Cell Nucleus | Cell Export - Exocytosis | Cell Import - Endocytosis | Cytoskeleton Introduction | Cytoskeleton - Microfilaments | Cytoskeleton - Microtubules | Cytoskeleton - Intermediate Filaments | Cell Mitochondria | Cell Junctions | Extracellular Matrix 1 | Extracellular Matrix 2 | Cell Cycle | Cell Division | Cell Death 1 | Cell Death 2 | Signal 1 | Signal 2 | Stem Cells 1 | Stem Cells 2 | Development | 2015 Revision
Laboratories: Introduction to Lab | Microscopy Methods | Preparation/Fixation | Cell Knockout Methods | Cytoskeleton Exercise | Immunochemistry | Project Work | Confocal Microscopy | Tissue Culture | Stem Cells Lab | Microarray Visit
Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G