Cell-Cell Interaction(Part 1: Cell Junctions)

Varij Nayan1 and Anuradha Bhardwaj21 Scientist, CIRB, Hisar-125001, Haryana, INDIA

2 Scientist, NRCE, Hisar-125001, Haryana, INDIA

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Tree of Life !!!

“ Whole being greater than the sum of individual parts”

“Of all the social interactions between cells in a multicellular organism, the most fundamental are those that hold the cells together”

Cell Signals one another with chemicals (Cell Signalling) Integration of cells into tissues : Cell surface Proteins Mediates Cell-Cell Interactions

Expression of Cell IdentityCell-Cell Adhesion- CAMsCell-matrix adhesion

CAMs and ECM can bind cell together, and transfer of information between the exterior and interior cells.

Cell-Cell Interactions

cellular coat Protection- water loss and wear

& tear Seal surfaces Regulate flow of materials

Different types have different Functions

Cell junctions key to formation and

maintenance of epithelial sheets

Mechanical stresses-transmitted by cytoskeletal filaments –anchored to cell-matrix

& cell-cell adhesion

Extracellular matrix directly bears mechanical stresses

Molecular Biology of the Cell (2008, Garland Publishing) and Molecular Cell Biology (2004, W H Freeman)

Major Adhesive Interactions

Molecular Biology of the Cell (2008, Garland Publishing)

Major Adhesive Interactions

Molecular Cell Biology (2004, W H Freeman)

Major Adhesive Interactions

Molecular Biology of the Cell (2008, Garland Publishing)

……………. Adhesive Interactions

Molecular Cell Biology (2004, W H Freeman)

Transmembrane Adhesion Proteins

Molecular Biology of the Cell (2008, Garland Publishing)

Cell Adhesion Molecules (CAMs)

Ca2+

independent

Don’t bind each other

Molecular Cell Biology (2004, W H Freeman)

Cell Adhesion Molecules (CAMs)

Name Main Location

Classical (are major components of cell-cell adhesion)

E- Cadherin Expressed on early embryonic cells in mammals. Later becomes restricted to embryonic and adult epithelial tissue

N- Cadherin First mesodermal, later CNS (Neurons, heart, skeletal m., kens and fibroblast)

P- Cadherin Trophoblast cells (Placenta), epidermis, breast epithelium

VE- Cadherin Endothelial cells

Cadherins- Classical Vs Non-Classical

Desmocollin Skin

Desmoglein Skin

T-Cadherin Neurons, muscle and Heart

Cadherin-23 Inner year, other epithelia

Fat (Drosophila)

Epithelia and CNS

Fat-1 (Mammals)

Epithelia and CNS

α, β and γ- Protocadherins

Neurons

Flamingo Sensory & some other epithelia

Non-Classical Cadherins

Desmosomal

Lacks a transmembran

e domain

a Seven-Pass Transmembrane Cadherin

Cadherins and Cell-Cell Adhesion The C-terminal

cytoplasmic domain associates with

cytoskeleton

The N-terminal extracellular domains

form dimer and through homoplilic interactions, form

tetramers

Molecular Biology of the Cell (2008, Garland Publishing)

The cells segregate according to the cadherins they express

Cadherins and Cell-Cell Adhesion

Molecular Biology of the Cell (2008, Garland Publishing)

Cadherin-dependent cell sorting

Cadherins and Cell-Cell Adhesion

Molecular Biology of the Cell (2008, Garland Publishing)

At eight-cell stage, begin to express E -cadherin

Compaction of an Early Mouse Embryo

Molecular Biology of the Cell (2008, Garland Publishing)

Cadherins mediate Ca2+ -dependent homophiliccell-cell adhesion

Extracellular domains of a classical cadherin (C-cadherin)

Molecular Biology of the Cell (2008, Garland Publishing)

Ca binds in the hinge regions between cadherin domains, and prevent the flexing.

Without Ca the molecule is floppy and adhesion fails

Cadherins mediate Ca2+ -dependent homophiliccell-cell adhesion

Molecular Biology of the Cell (2008, Garland Publishing)

Hook and Loop Fasteners

Velcro !!!

Many cadherin molecules are in a junction, functioning like a Velcro.

Molecular Biology of the Cell (2008, Garland Publishing)

Epithelial-mesenchymal transition

In mesenchymal cells the adhesion molecules are switched off. The transition is regulated by gene regulatory components named Slug, Snal and Twist. They affect E-cadherin expression Twist suppresses E-cadherin. It is involved in malignant transformation.

Linkage of classical cadherin to actin filaments

Molecular Biology of the Cell (2008, Garland Publishing)

Protein constituents of typical adherens junction

Molecular Cell Biology (2004, W H Freeman)

Desmosome

Anchor Proteins

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Biology of the Cell (2008, Garland Publishing)

Level of p120-catenin regulates cell junctions Beta-catenin - wnt-signalling Flamingo - as a GPCR VE-cadherin - for response to VEGF

Cell-cell junctions signalling

mediate cell-cell adhesion in the bloodstream

bind carbohydrates (lectins)

Selectins

Molecular Biology of the Cell (2008, Garland Publishing)

Leucocyte- endothelial cells interactions

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Cell Biology (2004, W H Freeman)

The Ig-superfamily members mediate Ca-independent cell adhesion.

ICAM and VCAM (Cellular Adhesion Molecules) bind integrins

Other types may have homophilic binding

Immunoglobulin superfamily

Molecular Biology of the Cell (2008, Garland Publishing)

Integrins: cluster into adhesive strs. In nonepithelial cells

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Cell Biology (2004, W H Freeman)

Molecular Cell Biology (2004, W H Freeman)

Fibronectin binding to Integrin

Molecular Cell Biology (2004, W H Freeman)

Tight Junctions

Molecular Cell Biology (2004, W H Freeman)

Gap Junctions

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Biology of the Cell (2008, Garland Publishing) and Molecular Cell Biology (2004, W H Freeman)

Summary

Molecular Biology of the Cell (2008, Garland Publishing)

ECM of Epithelial Sheets- basal lamina, collagen, laminin, proteoglycansECM of Nonepithelial Tissues- fibrillar collagens, association of hyaluronan and proteoglycans, fibronectinsPlasmodesmataCell Signalling

More Reading………..

“ Were the various types of cells to lose their stickiness for one another and for the supporting extracellular matrix, our bodies would at once disintegrate and flow off into the ground in a mixed stream of cells.”

Warren Lewis (1922)

Thank You