Cell Junctions

From CellBiology
Epithelial Cell Junction Types


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.

2017 Lecture Announcement

To start audio, click the start triangle above.

Due to a teaching double booking announced in the Tuesday Practical class, I am providing an earlier audio recording of the adhesion lecture along with the current lecture information on this page. Note that you can start the audio on the left and then scroll down the page to complete the lecture. This content will still form part of the examinable material for the final theory exam. (Play audio | MP3 file for download)

Note the Thursday lecture on Mitochondria will be presented as scheduled.

See also ANAT3231 Group Projects 2011

2011 Junctions: Synaptic Junctions | Gap Junctions | Tight Junctions | Desmosomes | Adherens Junctions | Neuromuscular Junction


  • 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


Molecular Biology of the Cell 4th ed. - V. Cells in Their Social Context Chapter 19. Cell Junctions, Cell Adhesion, and the Extracellular Matrix



Epithelial Cell Junctions

Below are some example historical research finding related to cell junctions from the JCB Archive. (Students note that the history is provided only as background for the lecture topic)

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.

Why Adhesion?

  • 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
  • Adhesion strength can be strong or weak as well as dynamically altered (as in migrating cells)
  • 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


Bacteria adhesin.gif

  • Prokaryotes adhesion molecules usually termed "adhesins"
  • occur on pili (fimbriae), flagellae, or the cell surface
  • adhesion first step in colonization

Unicellular Eukaryotes

  • express multiple adhesion molecules for nutrition, migration and pathogenesis
  • malarial parasite (Plasmodium falciparum) to bind to

Multicellular Eukaryotes

  • Maintains body form and structure
  • Tissues organized during development
  • Can be used for cell migration
  • Cell signalling alteration in disease
  • Large number of different transmembrane proteins forming cell - cell and cell - extracellular matrix junctions
  • Link to cell cytoskeleton or form communication channels between cells
  • Cell adhesion involved in signaling processes

Types of Adhesion

  • Cell-cell
  • Cell-extracellular matrix

Cell adhesion summary.png

Adhesive Functions

  • Basal lamina assemble and organize epithelia
  • Smooth muscle
    • Maintains integrity during contraction
  • Binds growth factors
    • Neurons growth cone guidance, fasiculation
  • Cell Migration (see blood cell migration model)
    • Development - migration, cell sorting, tissue development
    • Transmigration, wound healing, macrophages

YouTube Links: Transmigration | detailed explanation

Adhesion Characteristics

  • Transmembrane glycoproteins
  • Normally permanent
  • Except migrating cells and embryonic
  • Changes with development
  • Cells loose adhesion when mature or disease conditions. (see Erythrocytes, cancer)

Types of Adhesion Molecules

Each type of junction involves specific adhesion molecules embedded in the cell plasma membrane.

  • Cadherins
  • Immunoglobulin Superfamily
  • Selectins
  • Connexins
  • Integrins


  • The cadherin superfamily comprises classical and non-classical cadherins
  • present in all multicellular animals
  • mediate calcium ion (Ca2+) dependent cell-cell adhesions
  • more than 180 members in humans
  • Classical cadherins
    • (e.g.: E-cadherin, N-cadherin and P-cadherin) contain 5 cadherin repeats
  • Require calcium ions to bind
  • Homophilic binding through end element
  • Like with like
  • Functional unit a dimer
  • Non-classical cadherins
    • (e.g. desmosomal cadherin, protocadherins and T-cadherins) are more distantly related in sequence
  • Varying number of cadherin repeats
  • Some non-classical cadherins have primarily a signalling function

Immunoglobulin Superfamily

  • Vertebrates have 100+
  • In addition to adhesion they also have role in immune system
  • Contain varying number of Ig-related domains
  • G. Edelman - Nobel Prize in Physiology or Medicine in 1972
    • "for their discoveries concerning the chemical structure of antibodies"
    • studying the nervous system
    • Cell Adhesion Molecules (CAMs) family - Neuronal cell adhesion molecules (N-CAM) N-CAM, Ng-CAM L-CAM, I-CAM (Review - PMID 15550947)


  • Cell Surface carbohydrate-binding proteins
  • Vertebrates have only in circulatory system
  • Role in inflammatory response: adhesion of leukocytes (blood cells) to endothelium (vessel wall)
  • Cooperate with integrins and Ig-SF receptors
  • Selectins 2 Heterophilic interactions
  • Bind counterreceptors
    • L-selectin on white blood cells
    • P-selectin on blood platelets and on endothelial cells that have been locally activated
    • E-selectin on activated endothelial cells
Transmigration1.jpgWhite blood cell migrating out of a blood vessel (EM)


  • Mammals have genes for 18 alpha and 8 beta integrins
  • Role in cell adhesion to extracellular matrix (ECM) basement membranes
  • Induction of cell polarization by adhesion
  • Cell migration through ECM will discuss in ECM lecture
  • Glycosylated proteins
  • Bind through C terminal lectin domain of selectin
  • Comprising sandwich of beta sheets
  • Held together by hydrophobic interactions

  • Mainly receptors for ECM proteins
  • Fibronectin, laminin, collagen
  • Some heterotypic binding Ig superfamily
  • Interact with cell cytoskeleton
  • key component in signalling

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. These junction types also have histological names (and histological traditional names in brackets you will have heard in Histology classes).

  • Desmosomes (macula adherens)
  • Adherens Junctions (zonula adherens)
  • Septate Junctions
  • Tight Junctions
  • Gap Junctions
  • Tunneling nanotubes - this is a new type of cellular connection.
Metazoan intercellular junctions.jpg

Metazoan intercellular junctions


  • Discovered by K.R. Porter in 1954
  • intermediate filaments anchor the dense plaque that occurs under the membrane of each cell
  • desmos = bond
  • skin, lining of internal body cavity surfaces
  • disappear when cells are transformed


  • cell anchored to extracellular matrix (Hemi = half)
  • Present in tissues subject to shear or lateral stress

Adherens Junctions

  • microfilaments (MF) anchor the plaque that occurs under the membrane of each cell
  • plaques not as dense also occur as hemi-form
  • heart muscle, layers covering body organs, digestive tract
  • transmembrane proteins
  • Cadherin

Septate Junctions

  • Discovered by R.L. Wood 1959
  • found in invertebrate tissues - adhesion, sealing, communication
    • vertebrates do not have these junctions
  • septa = walls, regularly spaced cross bars 15-17 nm

Septate junction EM.jpg

Tight Junctions

Tight junction3.jpg
  • Discovered by M.G. Farquhar and G.E. Palade in 1963
  • Fusion of 2 plasma membranes acts as a “seal”
  • located on epithelia linings
    • digestive system gut, ducts, cavities of glands, liver, pancreas capillary walls urinary bladder
  • located in the central nervous system
    • blood-brain barrier (brain capillaries) and choroid plexus (modified cuboidal epithelium)
Schematic representation of tight junctions between two adjacent cells..jpg
  • zonula occludens formed by three main transmembrane protein types:
    • occludin, claudin(s) and junctional adhesion molecule-1 (JAM-1)
  • adhesion proteins are linked to the actin cytoskeleton (MF)

Gap Junctions

Gap junction1.jpg
  • Discovered by J.P. Revel & M.J. Karnovsky in 1967
  • used for rapid communication
    • heart muscle, smooth muscle, embryo blastocyst cells, electrical and chemical integration as a single functional unit
    • Also in embryonic development
  • direct communication between cells (open & close) of signaling molecules
    • ATP, cyclic adenosine monophosphate (cAMP), inositol triphosphate (IP3), glucose, glutathione, glutamate, sodium, potassium and calcium ions.
  • close membranes 2 - 3 nm apart
  • main transmembrane protein - connexins
  • two hemichannels (connexons) - form hollow 1.5 nm diameter cylinders
  • each formed from 6 connexin molecules
  • rapidly turned over
Electron Micrograph Filtered Image of Two Connexons.jpg

Electron Micrograph Filtered Image of Two Connexons

Gap junction5.jpg

Tunneling nanotubes

  • 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

An epithelial cell would typically have different junctions between each cell (lateral wall) and with the underlying basement membrane ECM (basal wall).
  • Tight Junction - seals neighbouring cells.
  • Adherens Junction - joins actin bundles between cells.
  • Desmosome - joins intermediate filaments between cells.
  • Gap Junction - cell-cell communication (signalling), passage of small molecules.
  • Focal Adhesion - anchors microfilaments to ECM
  • Hemi-desmosome - anchors cell intermediate filaments to ECM (basal lamina in epithelia, ECM CT)
Cell adhesion summary.png

Epithelial Cell Junction Types

Extracellular Matrix

Adhesion cell ecm2.jpg
  • Extracellular Matrix (ECM) formed by substances secreted (exocytosis) by cells lying outside the cell membrane
  • When cell junctions bind to ECM rather than a cell they form a "hemi" or half junction.
  • Specific ECM glycoproteins interact with these cell adhesion proteins.

Note - Extracellular matrix will be covered in detail in a later lecture.


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

Fl focaladhesion.jpg

focal adhesions

  • links the outside of the cell (ECM) through transmembrane proteins (integrins) with the cell cytoskeleton (actin microfilaments)
  • (or inside the cell outward) actin cytoskeleton - integrins - extracellular matrix
  • Important for tissue integrity and cell migration.

Adhesion cell ecm2.jpg

Focal adhesion Migrating Cell
  • Adhesion closely coupled with the protrusions of the leading edge of the cell (filopodia and lamellipodia).
    • discussed in this week's practical class.
  • 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.
Focal adhesion migrating cell.jpg

Focal adhesion migrating cell

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 PMID27872252.jpg

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

palmoplantar keratoderma

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

The Cell- A Molecular Approach

Cooper, Geoffrey M. Sunderland (MA): Sinauer Associates, Inc.; c2000

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  • Tight junctions/adherens junctions: basic structure and function. Niessen CM. J Invest Dermatol. 2007 Nov;127(11):2525-32. Review.. PMID: 17934504
  • 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


Working Area

Adhesion Images

A series of micrographs showing adhesion junction images. Adhesion Junction Images | Cell Biology Images | New Images

There is also a gallery of all images added sorted by date New Images (the search option will only search by image file name).

2017 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 | 2017 Revision

2017 Laboratories: Introduction to Lab | Fixation and Staining |

2017 Projects: Group 1 - Delta | Group 2 - Duct | Group 3 - Beta | Group 4 - Alpha

Dr Mark Hill 2015, UNSW Cell Biology - UNSW CRICOS Provider Code No. 00098G