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UNSW Cell Biology

2008 ANAT3231 Lecture 08 - Cell Junctions

Introduction

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.

Lecture Text: Lecture Word Document (182 Kb)

Lab 5: Immunochemistry 

 

 

Cell Adhesion

Page Links: Introduction | Objectives | Lecture Audio | Textbooks | Abnormalities | References | Online Textbooks | Web Links | Web Movies | 2007 Lecture Slides | Comments Acronyms

Objectives

Lecture Audio

The University has a system for automated recording of lectures called Lectopia (or iLecture).

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Links: Lectopia Login Page | Cell Biology Podcast Page | Current Course Outline 2008

Why Adhesion?

Prokaryotes

Unicellular Eukaryotes

Multicelluiar Eukaryotes

Types of Adhesion

Adhesive Functions

Links: Image: Cell-Cell Adhesion in Leukocyte Transmigration | Movie: Cell-Cell Adhesion in Leukocyte Transmigration

Adhesion Characteristics

  • Transmembrane glycoproteins
  • Normally permanent
  • Except migrating cells and embryonic
  • Changes with development
  • Loose adhesion when mature or disease
  • Erythrocytes, cancer
   

Types of Adhesion Molecules

  • Cadherins
  • Immunoglobulin Superfamily
  • Selectins
  • Gap Junctions
  • Integrins

Cadherins

Cadherins

  • Contain 5 cadherin repeats
  • Each comprising sandwich of beta sheets
  • requires calcium ions to bind
  • Homophilic binding through end element
    • Like with like
  • Functional unit a dimer
   

Cadherins

Immunoglobulin Superfamily

  • Vertebrates have 100+
  • In addition to adhesion they also have role in immune system
  • Contain varying number of Ig-related domains
  • Comprising sandwich of beta sheets
  • Held together by hydrophobic interactions
   

Immunoglobulin Superfamily

  • 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

 

NCAM
http://nobelprize.org/nobel_prizes/medicine/laureates/1972/index.html

Neuronal cell adhesion molecules

(Image: Stress, cognitive impairment and cell adhesion molecules, Carmen Sandi, Nature Reviews Neuroscience 5, 917- (December 2004) doi:10.1038/nrn1555)

Selectins

  • Vertebrates have only in circulatory system
  • Role in adhesion of leukocytes (blood cells) to endothelium (vessel wall)
  • Cooperate with integrins and Ig-SF receptors
  • Selectins 2 Heterophilic interactions
  • Bind counterreceptors
  • Glycosylated proteins
  • Bind through C terminal lectin domain of selectin
Transmigration

Integrins

  • 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 will discuss in ECM lecture
   

Integrins

Cell Junction Types

  • Desmosomes (macula adherens)
  • Adherens Junctions (zonula adherens)
  • Septate Junctions
  • Tight Junctions
  • Gap Junctions

Epithelial Junctions

   

EM Desmosomes

EM Desmosome

EM Desmosome

Desmosomes

  • 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
Desmosome
TEM Desmosome

Links: Desmosome Structure and EM | Expression pattern of desmosomal components in the epidermis | human desmosomal disorders |

Hemi-Desmosome

Adherens Junctions

  • 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
  • transmembrane proteins
  • Cadherin
Adherens Junctions
 

Adherens Junctions

Septate Junctions

TEM Septate JunctionSEM Septate Junction

Tight Junctions

  • Discovered by M.G. Farquhar and G.E. Palade in 1963
  • zonula occludens
  • Fusion of 2 plasma membranes acts as a “seal”
  • Epithelia lining
  • digestive system gut, ducts, cavities of glands, liver, pancreas capillary walls urinary bladder
   

Gap Junctions

  • Discovered by J.P. Revel & M.J. Karnovsky in 1967
  • allowing direct communication between cells (open & close)
  • close membranes 2 - 3 nm apart
  • connexins form hollow 1.5 nm diameter cylinders
  • heart muscle, smooth muscle electrical and chemical integration as a single functional unit
  • Also in embryonic development
Gap Junction
  • gap junction
  • two hemichannels (connexons)
  • each formed from 6 connexin molecules
  • rapidly turned over
Gap Junction

Junctions Overview - Typical Epithelia

Cell Adhesion    

Tight Junction

seals neighbouring cells

Adherens Junction

joins actin bundles between cells

Desmosome

joins intermediate filaments between cells

Gap Junction

cell-cell communication, passage of small molecules

Hiemidesmosome

anchors cell intermediate filaments to to basal lamina (extracellular matrix)

 

Extracellular Matrix

Integrins

  • 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
Cell ECM Adhesion
   

Focal Adhesions

  • links the outside of the cell (ECM) through transmembrane proteins (integrins) with the cell cytoskeleton (actin microfilaments)
  • extracellular matrix
  • integrins
  • actin cytoskeleton

Focal Adhesions

Focal Adhesions (red) Actin microfilaments (green)

 

(Image: Christoph Moehl)

Abnormalities

Desmosomes

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)

Oncogenesis

not the cause but transformed cells loose adhesion, able to "break away" and spread (metastisis).

Links: Cadherin Knockouts | human desmosomal disorders | NCBI - Genes and Diseases | NCBI - OMIM |

References

There is a complete list of online textbook links at 2008 ANAT3231 Lecture 08 - Cell Junctions - References

Web Links

Web Movies

Molecular Cell Biology

First link is directly to Quicktime move, followed by associated textbook figure with legend. Look at the movie first, then look at the labelled image.


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Acronyms

2007 Lecture Slides

(MH - note that content will not match exactly current lecture structure but has been selected as having similar content)

lecture04 1 slide/page (view only) (53 pages, 1 Mb)

lecture04 6 slides/page (print) (9 pages, 516 Kb)

lecture04 outline (print no images) (6 pages, 92 Kb)

See also Lecture Slides Text on this current page

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Comments

 

In 2008 a new way of presenting course content online is being trialled. Please let me know of any difficulties/suggestions or things that work well.

Notice also that in some slides I have added annotations in brackets with my initials (MH - )

 

Links: Current Course Outline 2008