INTER CELLULAR JUNCTIONS

& CELL ADHESION

MOLECULES

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

Desmosomes & Hemidesmosomes

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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