Download Cellular Adhesion and Tissue

Cellular Adhesion and
Tissue
Ahmed A. Mirza, PhD,
MT(ASCP)
Outline

Introduction

Importance of adhesion in

Tissue development

Differential cell hypothesis

Cell junctions

Anchoring molecules

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Cadherins
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Integrins
Cell migration
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CAMs and Selectins
Clinical relevance of adhesion
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Homeostasis

Infection
Cellular Adhesion
Lecture Objectives
By the end of this lecture the student should be able to:
– Define the Differential cell affinity hypothesis
– Give an example to describe the hypothesis at work
– List the four types of junctions in the cell and discuss their functions
– Describe the function of their components
– Know the difference between the junctions and be able to identify them visually
from a figure
– Define CAMs and their superfamilies
– Discuss the functions and the role of Integrins, cadherens, and selectins
– name examples of: Integrins, cadherens, selectins
– The role of CAMs in cell migration
– List possible pathologies of defection in CAMs
Introduction

Varying degrees of cell-to-cell
adhesion

Very strong (found in tissue) to very
transient (found in WBC)
 Different molecules with different tasks
 Found everywhere in the body
 Changing level of expression based on:


Cell cycle and differentiation
Outside factors and ligands
Examples...

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Platelets aggregation at a wound site
Migration of white cells or monocytes into a site
of infection
Migration of osteoblasts to repair bone
Importance of Adhesion

Tissue formation

In order for tissue to be formed, early cells of similar
type must come together to develop into a
functional tissue

Different tissue forms due to a process explained by
the Differential cell affinity hypothesis or Differential
Adhesion hypothesis.
What is this hypothesis?
According to this hypothesis, cells congregate
near other similar cells with similar adhesion
molecules to maximize the bonding (adhesion)
strength between cells by creating a more
hermodynamically stable (less energy costing)
tissue or structure.

And even if we purposely mix the cells of different
germ layers (epidermal and neural in the figure
below), they will eventually find their like and
congregate to for two separate entities
In other words:


Cells could have the same type of “glue”
on their surface. The amount of “glue” or
its different distribution on the cell could
cause differences in the number of stable
connections between cells and their
different types.
Accordingly, the differences in strength of
cohesion between cells is caused by the
types and numbers of adhesion molecules
on expressed on cell surfaces.
Example:
Tissue of early stages of embryo development –
the separation of the ectoderm from the neural
tube and formation of the neural tube. Cells
expressing certain molecules on their surface
come together.
Cell junctions
Four functional classes of cell junctions in animal
tissues:

Anchoring junctions

Provide structure and strength to epithelial cells

Transmit stresses by pulling on the cytoskeleton

Some can stand higher stress on the tissue (e.g.,
connective tissue)

Two types: cell-to-cell and cell-to-matrix

Cell-to-cell: two structures



Cell-to-matrix: actin-linked and hemidesmosomes


Adherens: forms anchoring points that connects the cell
wall of one cell to that of the adjacent one
Desmosomes: forms anchoring points that connects
components of the cytosceleton of the cell to the adjacent
one
Both anchor the cell filements to the extracellular matrix
Important molecule families: cadherins, integrins

Occluding junctions (tight junctions)





Establishes polarity (apical/basal)
Prevent backflow from one side of the epithelial
layer to the next
Important molecules :
Channel-forming junctions (gap junctions)


Seal gaps between cells to make them impermeable
(e.g., intestine)
Link cytoplasms of adjacent cells
Signal-relaying junctions

Synapses in nervous system
Junction summary figure…
Adhesion Molecules
Transmembrane adhesion proteins link the
cytoskeleton to extracellular structures:

Cell-cell adhesions (cadherins)

Cell-matrix adhesions (integrins)

Internal linkage to cytoskeleton (intracellular
anchor proteins)
Cadherins
The cadherin superfamily includes hundreds of
different proteins:


Take their name from their dependence on
calcium
Extracellular domain has multiple copies of the
cadherin motif

Intracellular domain that varies

Adhesive and signaling functions

Forms strong binding from many repeats
attaching at the same time – like “Velcro”
Integrins





Involved in cell-extracellular matrix adhesion and
cell-cell adhesion
Structure: heterodimer consisting of two
transmembrane glycoprotein subunits (α and β), which
are non-covalently bound.
Both subunits contribute to ligand binding.
About 18 α subunits and 8 β subunits have been
identified, giving ~24 unique integrins.
Integrins are necessary during early development
such as fertilization, gastrulation, implantation, vessel
formation and other processes, but also during
migration (discussed later)
Anchoring molecules summary…
Cell Migration
Cellular migration is a very complex process
CAMs
• Cell adhesion molecules (CAMs) are proteins on
the surfaces of cells (such as WBC) to
endothelial cells, to each other or to the
extracellular matrix.
• Three superfamilies: Immunoglobulin, integrin
and selectin families
• The extracellular domains of these molecules
trigger a reaction inside the cell that will lead to
an immune response or regulation of one
• Examples: ICAM (intercellular), VCAM
(vascular), P-selectin
Selectins



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Selectins play a role in WBC migration from blood
vessels into the tissues during inflammation.
Different adhesion molecules are involved at each
stage.
At the inflammation site, endothelial cells express
seletins on the surface, which bind to molecules on the
WBC and bring it down to a slow role, but not
stopping.
Eventually stronger binding by specifically expressed
integrins on the WBC will bring it to a stop and attach it
to cells at the inflammation site
Finally the WBC traverse into the tissue
Clinical Relevance
Cell-cell junction problems…
• Desmoplakin mutation (in the demosome)
• Keratoderma,
• nail dystrophy
• cardiomyopathy
Integrin problems…
• Human Luekocyte adhesion deficiency
• Lack of integrin beta-2 (CD18)
• Increased bacterial infection after birth
• Glanzmann’s thrombasthenia
• defected integrin αIIbβ-3
• Increased mucosal bleeding
References
• Molecular Biology of the Cell (Garland science
2008)
• www.slideshare.net/kaj4/cell-adhesion-and-cellmigration. Accessed on 10/20/14
• http://www.rndsystems.com/MiniReview_MR96_
AdhesionMolI.aspx. Accessed on 10/23/14