INTRODUCTION Of all the social interactions between
cells in multicellular organism, the most fundamental are those that hold the cells together.
Many cells in tissues are linked to one another & to Extracellular Matrix at specialized contact sites called “CELL JUNCTIONS.”
Classification of Cell JunctionsI. Cell-cell Junctions Tight junctions, Gap junctions,
Desmosomes Adhesion belt / zonula adherensII. Cell-matrix junctions Focal contacts / adhesion plaques Hemidesmosomes
Classification as in Review of Medical Physiology by GanongI. Junctions that fasten cells to one another & to surrounding tissues Tight junctions, Adhesion belt, Desmosomes, Hemidesmosomes Focal adhesionsII. Junctions that permit transfer of ions & other molecules from one cell to another Gap junctions
Classification as in Alberts Molecular Biology of CellCell Junctions can be divided into 3 functional
groupsI. Occluding Junctions : Tight JunctionsII. Anchoring Junctions : Desmosomes, Hemidesmosomes, Focal
adhesions & Zonula adherensIII. Communicating Junctions : Gap Junctions
Tight Junctions / Zonula occludens• Surround apical margins of cells in epithelia
• Made up of ridges
• Degree of leakiness varies
• Composed of branching network of sealing strands
• Claudins & Occludins• ZO proteins
Adhesion Belt / Zonula Adherens
Connect actin filaments of two interacting cells
formed by cadherins
network contracts with the help of myosin motor proteins
Gap JunctionsCONNEXONS – hexagonal array of transmembrane protein units
Regulation of Gap junction communication• intra cellular calcium• PH
• voltage• extracellular signals
Functions of Gap Junctions1. In tissues containing electrically
excitable cells, coupling via gap junctions is very usefull
2. Role in non-excitable tissues3. Normal development of ovarian
follicles4. Role in Embryogenesis
Cell Adhesion Molecules Attach cells to basal lamina & to each other
Are Transmembrane receptors with 3 domains : intracellular, transmembrane & extracellular
Mediate both Homophilic & Heterophilic binding
CAMs can be divided into 4 major families1. Cadherin superfamiliy2. Selectins3. Integrins4. Immunoglobulin superfamilyOther way of classifying CAMs is,I. Calcium-dependent Cadherins Selectins IntegrinsII. Calcium-independent Ig superfamily
CADHERINSMediate homophilic bindingStructure contains a short transmembrane
domain & a relatively long exrecellular domain wit 4 cadherin repeats (EC1 to EC4) each with a calcium binding sequence.
Interact with CateninsTypes :N-cadherinP-cadherinE-cadherin
SELECTINSCalcium dependent carbohydrate binding
proteinsMediate initial attachment of leukocytes to the
endothelium on the blood vessel wall during rolling step of Phagocytosis
Structure includes a NH2-terminal C-type Calcium binding lectin domain, a membrane spanning domain & a short cytoplasmic domain
Mediate heterophilic bindingTypes:L-selectinP-selectinE-selectin
INTEGRINSAre principally involved in cell-matrix adhesionAlso act as regulatory receptors that can initiate
intracellular signal pathwaysComposed of hetero dimers consisting of 2 non-
covalently associated subunits α and βBoth subunits are membrane glycoproteins with a
large extracellular domain, a single transmembrane domain & a short cytoplasmic domain
Types :β 1 integrins – VLA proteinsβ 2 integrins – Leu CAMsβ 3 integrins – cytoadhesionsβ 4 integrins
IMMUNOGLOBULIN SUPERFAMILYMediate many different functions including
acting as receptors for growth factors & mediating cell-cell & cell-matrix interactions
Structure is characterised by repeated domains similar to those found in immunoglobulins.
Mediate both heterophilic & homophilic binding
Types :ICAMs – Intracellular CAMsVCAMs – Vascular CAMsPECAMs – Platelet Endothelial CAMsNCAMs – Neural CAMs
ICAMs• ICAM-1 (CD54), ICAM-2 (CD102) are counter
receptors for leukocyte β2 integrins• ICAM-1 is expressed on leukocytes, fibroblasts,
epithelial cells & endothelial cells• ICAM-2 has similar distribution but is not
regulated by cytokines as ICAM-1
VCAMs• VCAM-1 (CD106) is expressed on surface of
activated endothelium, dendritic cells, tissue macrophages & bone marrow fibroblasts
• It interacts with leukocyte integrin α4 β1 on eosinophils, monocytes & with α4 β7 on activated peripheral T-cells
PECAMs• PECAM-1 (CD31 or endoCAM) is found on
endothelial cells, on platelets, some monocytes & neutrophils
• Is involved in homophilic adhesion
NCAMs• Is expressed on most of the nerve cells• Play an important role in fine tuning of adhesive
interactions during development & regeneration“Although cadherins & Ig family members are
frequently expressed on the same cells, the adhesions mediated by cadherins are much stronger & are responsible for holding cells together, segregating cell collections into discrete tissues & maintaining tissue integrity”
APPLIED PHYSIOLOGY PEMPHIGUS
Role of Gap Junctions in Embryogenesis
E-cadherin & Prostate cancer
ICAM-1 & Melanoma
VCAM-1 & Tumour Metastases
REFERENCESReview of Medical Physiology by William
F.Ganong, 21st ed; 2003 by The McGraw-Hill Companies, Inc.
Alberts Molecular Biology of Cell 5th editionCell Junctions- Molecular Biology of Cell –
NCBI BookshelfCell Junctions- Biology Encyclopedia,
www.biologyreference.com/celljunctions.html#b
en.wikipedia.org/wiki/Cell _adhesion_molecule
Cellular Adhesion and Adhesion Molecules, Review Article by Zerrin Seller ; Turk Journal of Biology 25(2001)1-15
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