Difference between revisions of "2011 Group 4 Project"

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The afore mentioned cancers downregulate desmoplakin[11]and therefore in non pathological states the desmosomes, due to this component, aids in the regulation of cellular proliferation.
The afore mentioned cancers downregulate desmoplakin[11]and therefore in non pathological states the desmosomes, due to this component, aids in the regulation of cellular proliferation.

Revision as of 20:15, 9 May 2011


Desmosomes are a specialised feature of the cellular surface that allows for the adhesion between adjacent cells. These structures are transmembrane molecules that belong to the cadherin family.[1] Found primarily in the epithelium and cardiac muscle, desmosomes are effective in resisting mechanical stress as a result of their hyper-adhesive state. Adhesiveness can be increased and decreased as a response to protein kinase C signaling during processes such as wound healing.[2]


Early 19th Century : Light microscopes allowed for the detection of desmosomes within cells.

1864 : Giulio Bizzozero gives the first description of the desmosome. He commented on the small, dense areas that were seen between cells and suggested that these were points of adhesion between adjacent cells. [3] [4]

1920 : Josef Schaffer names the structure being seen under the microscope, 'desmosome.' From a greek origin, the name comes from two words meaning 'bond' and 'body.' [5]

1956 : After biological sciences were revived after the world wars, Porter viewed cells using electron microscopy to note that between adjacent cells there were electron dense areas that branched off into cells with fibrous strands. [6] [7]

1974 : By developing new techniques, Skerrow and Matoltsky isolated desmosomes from other cellular components. [8] After running biochemical tests to identify their molecular characteristics, the pair found that the structures had a high glycoprotein content, and that it was these glycoproteins that were responsible for the cell-cell interactions. In doing this, they were able to confirm the hypothesis from 30 years earlier, that desmosomes were in fact junctions between cells. [9] [10]

1981 : Franke and Steinberg characterized and purified the components of desmosomes. [11] [12] [13]

1983 : Using specific antibodies, Cowin and Garrod identify the localisation of desmosomes and note that desmosome distribution is similar between all vertebrates. [14] [15]

1985 : Steinberg, along with his colleagues, begin to isolate plaque proteins. [16] [17]

1988 : Green isolated and analyzed the desmoplakin coding sequence. [18] [19]

1990 : Blaschuk identifies that cadherins contain a tripeptide motif that is crucial in cell adhesion. [20] [21]

1990 Green analyses the amino acid sequence of desmoplaking protein. It was predicted that desmoplakin would have a central allpha-helical, coiled-coil region. [22] [23]

1990 : Koch isolated and characterised the cDNA encoding desmoglein. When screened with cDNA libraries, it was found that they had a high level of homology with cadherins, and as such identified it as a part of the cadherin superfamily. [24] [25]

1991 : Desmocollin, another transmembrane protein in desmosome is isolated and characterised by Collins. Desmocollin has an a form and b form within the cytoplasm, which are produced by alternative splicing of mRNA. [26] [27]

1992 : Stappenbeck and Green define the functional domains of desmoplakin. [28] [29]

1994 : Kouklis demonstrates that the interactions between desmoplakins and intermediate filaments are direct. [30] [31]

1997 : McGrath describes that mutations in Plakophilin-1 leads to ectodermal dysplasia. [32] [33]

1998 : Desmosomal cadherin attachments can be inhibited by peptides that correspond to desmocollin and desmoglein receptor sites (Tselepis). [34] [35]

1999 : Structural studies of the demoplakin gene confirm that the carboxyl terminus acts as an intermediate filament binding site (Kowalczyk). [36] [37]

2000 : Amagai explained the pathogenesis of S. aureus bullous impetigo which is caused by toxin-mediated damage to desmosomes. This was achieved by using antibody immunotherapy. [38] [39]

2001 : Vasioukhin saw that epithelial cells rely on desmoplakin for integrity. [40] [41]

2002 : Windoffer suggests that desmosome structure is dynamic, using fluorescence recovery. [42] [43]

Dynamic Structure of Desmosomes - Videos

2003 : Kljuic identifies the genes for desmogleins and desmocollins on the q arm of chromosome 18 in humans. [44] [45]

2003 : He generates a three-dimensional image of a desmosome. [46][47]

2004 : Grossman confirmed the necessity for plakophilin in desmosomal plaques. [48] [49]


--z3217345 11:02, 4 May 2011 (EST)

Please note permission was sought and granted for citing of PNAS Article: The three-dimensional molecular structure of the desmosomal plaque

Introduction to the Structure of Desmosomes

Desmosome originates from the greek terms desmo meaning bond and soma meaning body. [50] This etymology reveals the main function of desmosomes which is to bind cells to one another. [51] Desmosomes, also known as macula adhaerens, have a number of other roles including strengthening the internal structure of a cell, sensing environmental cues, regulating tissue homeostasis and assisting in tissue morphogenesis. [51] By indirectly connecting intermediate filaments of adjoining cells, they produce a strong adhesive force which can resist great shear forces. [50] Hence, they are found in such tissues as the myocardium, the bladder, the gastrointestinal mucosa and many epithelia. [52] To have a greater understanding of why desmosomes are located in these areas and how and why the above functions occur, one requires an understanding of the structure of desmosomes, which will be explained below.

Structure on a Cellular Level

Desmosome Electron Micrograph: Bovine Nasal Epidermis

The desmosome, 300nm in diameter, consists of two distinct domains - the extracellular core domain, ~30-35nm in diameter, and the dense cytoplasmic plaque, ~30-40nm in diameter. [52] The extracellular core domain, also known as the desmoglea, is made up of the transmembrane proteins - cadherins. [51] There are two types of desmosomal cadherins: desmogleins (DSGs) and desmocollins (DSCs). They extend from the plaque to the extracellular core where they connect to the adjacent cell's cadherins. The plaque, situated parallel to the inner leaflet of the cell membrane, is composed of an outer dense plaque and an inner dense plaque separated by a space of ~8nm. [52] The outer dense plaque is located closer to the plasma membrane than the inner dense plaque and links cadherin tails to desmosomal anchor proteins. [52] The linker proteins involved are plakoglobin (PG), plakophilin (PKP) and desmoplakin (DP). Extending out from the outer dense plaque are the desmosomal anchor proteins desmoplakins. These form the majority of the inner dense plaque. On the other side of the inner dense plaque is where the intermediate filament network of the cytoskeleton attaches. [53]

Structure on a Molecular Level

Desmosome Diagram

Extracellular Domain

As outlined above, the extracellular domain consists of desmosomal cadherins: desmogleins (DSGs) and desmocollins (DSCs). Cadherins are arranged along the mid-line in ~7nm intervals, with alternating cis (interaction between same cell surface) and trans (interaction between different cell surfaces) dimers causing a tightly packed zipper formation. They are each made up of four extracellular immunoglobulin domains (EC1-4), an immunoglobin extracellular anchor (EA), a transmembrane domain (TM), an intracellular anchor (IA) and additional cytoplasmic domains, which distinguish the cadherin isoforms. [52] Each immunoglobin domain is connected end to end by three calcium ions, forming a curved structure of about 100 degrees. Along the domains are disulfide bonds, O-linked sugars and N-linked sugars. [50]

The cadherin isoforms are composed of different additional cytoplasmic domains as follows [52]:

Desmosomal Cadherins Diagram
Detailed Cadherin Diagram - Image (g) Shows Cis And Trans Interactions


DSCb - short carboxy-terminal domain






There are three isoforms of DSC (1-3), however they splice alternatively into two transcript variants named DSCa and DSCb.

ICS is an intracellular cadherin-like sequence, which binds to plakoglobin.

IPL is an intracellular proline-rich linker.

RUD is repeat unit domains.

DTD is a desmoglein terminal domain

Tyrosinase-related protein 2 (Trp2) mediates the cis and trans interactions and is most probably responsible for the binding of cadherins to the plaque. [50] However it is currently unknown whether heterophilic cis and trans or homophobic cis and trans interactions are the main cause of cell adhesion. [54]

The extracellular domain mediates adhesion and whilst the mechanical structure is extremely strong, it is still dynamic since the attachment of both types of cadherins are reliant on Ca2+ levels. During embryonic development of the desmosome, the link between the two cells remains weak. Eventually the link strengths and the cell becomes hyperadhesive. This latter stage is calcium independent, as once protein kinase C is activated by Ca2+ it is able to remain activated in the long-term. Hence this hyperadhesive state will not be affected by changes in Ca2+ concentration. However the desmosome is able to revert to the earlier state when responding to certain environmental signals to allow for such things as cell migration if regeneration of the epithelia is necessary. [50] [51] The primary morphological attribute which indicates calcium independence is a distinct electron-dense midline that bisects adjoining cells' extracellular core domains. [55] Whereas when desmosomes are calcium dependent the midline is lost and the diameter of the intercellular space decreases by 10%. Potentially this is caused by Ca2+ ions becoming trapped to the cadherins and securing their position into an ordered structure. [55]

Outer Dense Plaque

The dense plaque is made up of two electron-dense zones: an outer dense plaque and an inner dense plaque. The outer dense plaque being lower in density that the inner dense plaque. They are separated by a electron-lucent zone, ~8nm in diameter. The outer dense plaque is located in the cytoplasm, parallel to the plasma membrane. [55] It is ~15-20nm in diameter and characterised by two zones: a ~4nm zone located ~10nm from the plasma membrane and a ~8nm zone located ~20nm from the plasma membrane. The major plaque proteins are plakoglobin (PG), plakophilin (PKP) and desmoplakin (DP).2146301

The structure of the major plaque proteins is as follows [52]:

Plakoglobin And Plakophilin Diagram
Desmoplakin Diagram

PG - Head, 12 arm repeats, Tail

PKPa - Head, 5 arm repeats, Insert, 4 arm repeats, Tail

PKPa - Head, 5 arm repeats, Insert, 4 arm repeats, Tail

DP1 - Head, Rod, C tail, GSR

DP2 - Head, Rod, C tail, GSR


Head is an amino-globular head domain with a N terminus.

Tail is a caboxy-terminal tail with a C terminus. In desmoplakin, the tail constits of three plakin repeat domains.

GSR is a glycerine-serine-arginine rich domain.

Insert is a rigid structure producing the bent angle.

The two isoforms of plakophilin, PKP1 and PKP2, both splice into PKPa and PKPb. PKPa is shorter in length than PKPb. For PKPb in comparison to PKPa: in arm repeat three PKP1 version has an additional 21 amino acids, and in arm repeat four PKP2 version has an additional 44 amino acids.

The isoforms of desmoplakin, DP1 and DP2, are characterised by the length of their rod domain - the DP1 rod being ~2/3 longer than the DP2 rod.

Plakoglobin and desmoplakin complexes form an alternating arrangement which acts as a base for the desmosomal cadherins to attach. The cadherin tails bind to the N terminus of desmoplakin before they connecting to the adjoining cells' desmosomal cadherins. Formation of this initial structure is mediated by plakoglobin and plakophilin. For reinforcement the remaining space between the plaque and the plasma membrane is filled by plakophilins. 21464301

Inner Dense Plaque

The inner dense plaque, alike the outer dense plaque, is ~15-20nm in diameter. [55] It is primarily comprised of the junctional complexes, desmoplakins, which tether to the intermediate filaments.


Desmosomes are important cellular adhesive components of epithelia. [[56]]

Shearing forces encountered in epidermis or cardiac tissue is withstood on the cellular level by these intercellular anchoring points.

Desmosomes contribute to confluent epithelial sheets [[57]]

Intercellular cell to cell desmosomal adhesion junctions contribute largely to the barrier function of epithelia and to the strength and integrity of this and other tissues in which they are found.[[58]]

Currently there are aspects of desmosomal structure that are unknown, however it is known that cytoplasmic surface molecular interactions link the desmosome extracellular cadherins with intracellular intermediate filaments.[6]

The attachment plaque mediates adhesion of intermediate filaments with the extracellular cadherin tails of the plasma membrane[7] Electron microscopy (EM) and specialised staining techinques suggest the manner in which the extracellular core domain (ECD) transmembrane homophillic cell-cell adhesion glycoprotein cadherins, namely desmocollin and desmoglein, bind to each other, zipper like, in the the midline between two cells.

It was further revealed that the tails of these calcium dependent cadherins then bind through the plasma membrane and into the cytoplasm of the bound cells to bond firmly with a cytoplasmic plaque mass located intracellularly in each cell that is being anchored by a desmosome formation.[8]

It is the proteins desmoplakin 1 and 2, plakoglobin and plakophilin that forms the cytoplasmic dense plaque that indirectly functions as the bondage to the intermediate filaments thus locking the extracellular cadherins with the interior of the cell by providing an anchoring point for both.[9]

Investigations into other cellular functions of the protein components of desmosomes have looked at the protein components individually away from them as a synergistic adhesive junction as a whole.

The desmoplakin of the dense plaque has been found to bind to desmoglein 1, but besides this function it has been implicated in the formation of microtubules within cells. During tumourous cancer growth, in such cancers as oropharyngeal and breast cancer, the desmoplakin's other function becomes somewhat unregulated and aids tumour growth by stimulating angiogenesis or the growth of new blood vessels from existing vascular structures.[10]

The afore mentioned cancers downregulate desmoplakin[11]and therefore in non pathological states the desmosomes, due to this component, aids in the regulation of cellular proliferation. k


Hemidesmosomes like the name suggests are extremely similar to the desmosomes in the fact that they are specialized junctional complexes. However unlike desmosomes which specialises in cell to cell adhesion hemidesosomes contribute to the attachment of epithelial cells to the underlying basement membrane in stratified and other complex epithelia, such as the skin, the cornea and both parts of the respiratory and gastrointestinal tract. Hemidesomosomes are multiprotein complexes and it is these proteins that help determine the cell – stromal coherence of the hemidesomoses. The proteins also provide the cells with cues critical for the polarization, the spatial organization and for tissue architecture. The functional activity can be modulated however the regulation of the adhesive interaction between the hemidesmosomes and the basement membrane below is essential in various normal biologic process, such as wound healing and tissue morphogenesis.

The function of a hemidesmosomes are regulated via many different factors for example extracellular matrix (ECM) proteins and growth factors. To add to this the 6 4 integrins in the hemidesmososme also act as regulatory components and this done by transducing signals that profoundly affect the cellular function. Thus hemidesmosomes are not only structural adhesion complexes but also serve as signalling devices via the 6 4 integrin which affecting cell phenotype.




Calcium ion levels are integral in junction assembly. In vitro, extracellular calcium levels have been found to trigger the formation of the junctions. [59] After cells that have been incubated in low calcium medium, were switched into a medium containing standard calcium concentrations, the formation of desmosomes was seen as soon as 5 minutes. [60] The deregulation of calcium levels within cells have been associated with junctional defects. Hailey-Hailey disease and Darier's disease are caused by defects in Golgi and ER calcium pumps. [61] These both lead to a loss of integrity in skin epithelium, due to a lack of cell-cell attachment via desmosomes. [62] [63]


It has been suggested that regulation of desmosome assembly is closely associated with the assembly of adherens junctions. [64] Desmoplakin is the only protein, so far identified, that is common to both junctions. In vitro, cells that did not express desmoplakin were unable to localise the proteins specific for the adherens junctions and the desmosomes. [65] Thus, it has been suggested that it plays a role in segregating the proteins relative to each junction and so affecting assembly.


Phosphorylation has been found to be largely involved in activating and deactivating desmosome assembly. It has been suggested that protein kinase C (PKC) is involved in the regulation of this action. [66] PKC inhibition is required for desmosome assembly to occur, that is, dephosphorylation encourages formation. Phosphorylation onto serine of desmoplakin by protein kinase C can lead to the disassembly of the cytoskeleton, junctions, and a loss of cell-cell contact. An increase in level of serine phosphorylation has also been linked with an increase in junction solubility of the desmoplakin. This suggests that phosphorylation may play an integral role in the dissociation of the desmosomal plaque from the keratin filaments. [67] The outcome of plakoglobin (an important desmosomal protein) is also largely dependent on its phosphorylation. [68]

Related Diseases

Bullous Impetigo

Impetigo is a skin condition common in school children, especially those who play close contact sports. This skin condition is also known as school sores and is caused by a bacterial infection. Bullous Impetigo causes fluid-filled blisters in the skin, primarily on the trunk, arms and legs. These blisters are painless and scab over before they heal. [69]

Staphylococcous aureas is the bacteria responsible for inducing bullous impetigo through its release of exfoliative toxins. When mice are injected with exfoliative toxin from S. aureas blistering of the skin is noticed and under an electron microscope it is possible to see that the desmosomes within the epithelia have been torn apart. [[70]] Exfoliative toxin A has been proven to cause the blistering through its serine protease activity. The blisters of Bullous Impetigo are localised to the superficial epidermis, and as such it is possible to confirm that the exfoliative toxin A is specific to Desmoglein-1. Desmoglein -1 is present not only in the superficial layers of epithelium but also in the deeper layers. Desmoglein-3 however is not present in the superficial layer. Given that blistering does not occur in the deeper layers it is possible to assume that Desmoglein-3 compensates for the destruction of Desmoglein-1. Experimental results have shown that on injection of exfoliative toxin A, Desmoglein-1 was damaged while Desmoglein-3 remained unaltered. This was done by addition of antibodies for Desmoglein-1 and Desmoglein-3 followed by immunoflurorescence. [71]

Bullous Impetigo has similar symptoms to many drug reaction symptoms. The differentiation between these is possible through a skin biopsy. Bullous impetigo will only have blistering on the superficial layers while a drug reaction will see blistering in the lower layers of the epithelium as well as necrotic keratinocytes. Treatment usually consists of a course of antibiotics but it is important to consider that antibiotic-resistant strains of S.aureas are quite common. [72]

Pathophysiology of Bullous Diseases - video

Palmoplantar Keratoderma

Desmoplakin is the most abundant protein in desmosomal plaques, therefore having an important role in linking the intermediate filaments to the plasma membrane of cells in the epidermis and heart. Palmoplantar Keratoderma is skin condition that results from a mutation on the gene that encodes desmoplankin. Mutations can either lead to a loss of the gene completely, or cause haploinsufficiency. This genetic disorder was noted in patients who were affected by this skin condition. [73]

Palmoplantar Keratoderma is a rare condition. It is characterised by hyperkeratosison the palms of the hands and soles of the feet. This leads to a distinctive thickening of the skin, often in a striated pattern. When viewed under a light microscope, affected areas showed an increase in space between the keratinocytes. Moreover, the desmosomes appeared to be smaller and less were found when compared to a normal section of skin from the same patient. [74]

Arrhythmogenic Right Ventricular Cardiomyopathy

Arrhythmogenic Right Ventricular Cardiomyopathy is a cardiomyopathy is related to the functioning of desmosomes. When cell adhesions are compromised, the cardiac tissue loses its integrity. As a result of this, the body attempts to repair the damage by replacing the tissue with fibrofatty tissues. This presents a number of problems for the cardiovascular system and results in some fatal complications. [75] This condition is more common in individuals under the age of 30. Clinical symptoms present with misarrhythmias or in some cases, sudden death. Most prominent symptoms are seen during or after intense physical activity when the heart is put under stress.

Current Research

Wide Spectrum of Desmosomal Mutations in Danish Patients with Arrhythmogenic Right Ventricular Cardiomyopathy (2010)

In the study, 65 unrelated patients with Arrhythmogenic right ventricular cardiomyopathy (ARVC), a lethal disease which is characterised by Ventricular tachyarrhythmias with right and/or left ventricular involvement and fibrofatty infiltrations in the myocardium were screened for mutations in the number of genes that code for desmosomes which include desmocollin-2 (DSC2), desmoglein-2 (DSG2), desmoplakin (DSP), plakoglobin (JUP) and plakophilin-2 (PKP2) and TGFb3. The results of the study was the identification of 19 different mutations with all genes that code for desmosomes being affected apart from TGFb3 which showed no genomic rearrangements or mutations. The conclusion of the study was that 33% of patients in this Danish cohort with ARVC carried desmosomal mutations with a surprisingly wide mutation spectrum. A substantial proportion of patients carried more than one mutation. Our study supports comprehensive desmosomal mutation screening beyond the first encountered mutation, whereas routine screening for genomic rearrangements does not seem indicated.[76]


Desmosome : An intercellular junction that is involved in cellular adhesion through attachment of cadherins.

Hemidesmosome : Specialized junctional complexes that attach epithelial cells to the basement membrane.

Cadherin : A transmembrane protein that is regulated by calcium ion concentrations for cell adhesion.

Desmocollin : A type of cadherin

Desmoglein :


Ectodermal Dysplasia

Antibody immunotherapy


Images and Videos

Pathophysiology of Bullous Diseases - video

[http://www.pnas.org/content/early/2011/03/30/1019469108.full.pdf The three-dimensional molecular structure of the desmosomal plaque]

Reference List

  1. [1]
  2. [2]
  3. Bizzozero G (1864) Delle cellule cigliate, del reticolo Malpighiano dell'epidermide. Annal Univ Med 190:110-8
  4. [3]
  5. [4]
  6. Porter KR (1956) Observations on the fine structure of animal epidermis. Proceedings of the International Congress on Electron Microscopy, London, July 1954. Royal Microscopical Society, London, p 539
  7. [5]
  8. [6]
  9. [7]
  10. [8]
  11. [9]
  12. [10]
  13. [11]
  14. [12]
  15. [13]
  16. [14]
  17. [15]
  18. [16]
  19. [17]
  20. [18]
  21. [19]
  22. [20]
  23. [21]
  24. [22]
  25. [23]
  26. [24]
  27. [25]
  28. [26]
  29. [27]
  30. [28]
  31. [29]
  32. [30]
  33. [31]
  34. [32]
  35. [33]
  36. [34]
  37. [35]
  38. [36]
  39. [37]
  40. [38]
  41. [39]
  42. [40]
  43. [41]
  44. [42]
  45. [43]
  46. [44]
  47. [45]
  48. [46]
  49. [47]
  50. 50.0 50.1 50.2 50.3 50.4 <pubmed>20672011</pubmed>
  51. 51.0 51.1 51.2 51.3 Molecular Biology of the Cell Alberts, Bruce; Johnson, Alexander; Lewis, Julian; Raff, Martin; Roberts, Keith; Walter, Peter New York and London: Garland Science; c2002
  52. 52.0 52.1 52.2 52.3 52.4 52.5 52.6 <pubmed>20066089</pubmed>
  53. <pubmed>20671997</pubmed>
  54. <pubmed>21098030</pubmed>
  55. 55.0 55.1 55.2 55.3 <pubmed>20626351</pubmed>
  56. http://www.ncbi.nlm.nih.gov/pubmed/20671997 20671997
  57. http://www.ncbi.nlm.nih.gov/pubmed/20671997 20671997
  58. http://www.ncbi.nlm.nih.gov/pubmed/20066089 20066089
  59. <pubmed>6209289</pubmed>
  60. [48]
  61. [49]
  62. [50]
  63. [51]
  64. [52]
  65. [53]
  66. [54]
  67. [55]
  68. [56]
  69. http://www.nhs.uk/conditions/Impetigo/Pages/Introduction.aspx
  70. http://www.ncbi.nlm.nih.gov/pubmed/15363804 15363804
  71. http://www.nature.com/nm/journal/v6/n11/abs/nm1100_1275.html
  72. John R. Stanley, M.D., and Masayuki Amagai, M.D., Ph.D. Pemphigus, Bullous Impetigo, and the Staphylococcal Scalded-Skin Syndrome. N Engl J Med 2006; 355:1800-1810October 26, 2006
  73. D. Keith B. Armstrong*, Kevin E. McKenna1, Patricia E. Purkis2, Kathleen J. Green3, Robin A. J. Eady4, Irene M. Leigh2 and Anne E. Hughes. Haploinsufficiency of Desmoplakin Causes a Striate Subtype of Palmoplantar Keratoderma. Human Molecular Genetics. (1999) 8 (1): 143-148.
  74. Neil V Whittock, Gabrielle H S Ashton, Patricia J C Dopping-Hepenstal, Matthew J Gratian, Fiona M Keane, Robin A J Eady and John A McGrath. Striate Palmoplantar Keratoderma Resulting from Desmoplakin Haploinsufficiency. Journal of Investigative Dermatology. (1999) 113, 940–946.
  75. http://content.onlinejacc.org/cgi/reprint/38/7/1773.pdf
  76. <pubmed>20864495</pubmed>

Coordinator Comment to all Groups

I will add a general comment that will be the same to all groups under this heading.

Referencing Extension Problem

--Mark Hill 13:16, 3 May 2011 (EST) As mentioned in the lecture, I am aware of the referencing extension problem on your project pages. I have the following temporary solution, of removing the extension, so that groups can continue to add content to their project pages. I am also giving everyone a 1 week extension before the peer assessment.

This should only be done if your project page is not allowing you to save changes!

A. The Easy Way....

The following 4 steps can be done on the webpage or select all content in edit mode, copy and paste into a text editor. All steps must be completed before you attempt to save.

  1. In page edit mode, find all <pubmed> reference tags.
  2. Replace this tag with [http://www.ncbi.nlm.nih.gov/pubmed/ Note, there should be no spaces between the internet address and the pmid number.
  3. Now find all </pubmed> reference tags.
  4. Replace this second tag with ]

This will generate a numbered reference list that we can later fix up.

B. The Better Looking Result....

Whatever is between the <ref> </ref></pubmed> tags is what will appear in your reference list, so you can format the reference and link to appear in your reference list.

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