Module 8: Cell Adhesion

Lecture 1: Cell Adhesion Molecules

Multicellularity: Stable Interactions between Cells
- Single fertilized egg multicellular organisms
- Development requires
o Reiterated mitotic divisions
o Cell differentiation that defines tissue-specific patterns of gene
expression
o Signaling between cells
o Cells are able to associated and maintain connections
- Embryogenesis: formation of the inner cell mass, forming the embryo
o As the number of cells increase, they separate into one of three
germ layers
Endoderm, ectoderm, mesoderm
o Cells must establish and maintain connections

Sponge Cells Sort and Re-associate

- Ability of cells to recognize and adhere to one other
demonstrated by H.V Wilson
- Cells of two species of sponges cells of each
organism were separated using a fine mesh and then
mixed together
- Cells from the same species recognized and
associated back together, cells from different
species did not associate
Embryonic Cell Association is Cell
Specific
- Johannes Holtfreter used
cells form a frog embryo
- Took cells from two different
germ layers during
development and separated individual cells
- Two different types of cells mixed together, cells from like tissues
recognized one another and associated mimicked the organization seen
in the original embryo
- How do like cells recognize and contact each other during
embryogenesis? How do they stay together?
o Requires a collection of transmembrane proteins that span the cell
cell adhesion molecules (CAMs)
o After aggregation, cells form specialized cell junctions that stabilize
cell-cell interactions and facilitate communication between adjacent
cells
Different Types of Junctions in Epithelial Cells
 - Epithelial cells connect to one another along lateral surfaces to form
epithelial sheets
o Forms inner lining of digestive system and outer layers of skin

- Epithelial sheets in the intestine

o Basal surface (bottom) is anchored to
extracellular structures that provide an underlying
structure that includes the basal lamina or
basement membrane
Adhesion complexes:
hemidesmosomes connects cells to the
extracellular matrix
o Apical surface (top) is organized into microvilli
that face the interior of the intestine
- 4 types of adhesion complexes connect the lateral
surfaces
o Desmosomes (c), adherens junctions (b), gap junctions (e)
and tight junctions (a)
Tight Junctions
- Tight junctions (zonula occludens): connect
adjacent epithelial cells just below the apical surface
o Seals off space between cells, preventing fluid
movement across the layer of cells
Restricts diffusion of small molecules
Prevents leakage of digestive enzymes
o Linear arrays of occuldin and claudin proteins
are closely arranged between neighbouring cells
o Not a single junction, but an accumulation of
structures that form a complete band between
cells
- TEM image: see where cells are pinched together
- EM image: freeze fracturing: cells instantly frozen in
liquid nitrogen and broken apart
o Fracture occurs at points of weakness lateral
surface between neighbouring cells
- Tight junctions
o completely prevents the diffusion of molecules in
the extracellular space between the cells (small
electron-dense molecule: lanthanum hydroxide)
diffusing in the extracellular space from the basal surface
epithelial sheet, limited at the tight junctions and can move no
further
Gap Junctions Animal cells
 - Directly links the cytosol of one cell to the cytosol of the adjacent
link
o Pinches and holds cell membranes together
o Integrates metabolic activities of all cells in a tissue
o Each channel is 1.5 2.0 nm in diameter, allowing the free
diffusion of up to about 1 kDa in size through the channels
o 6 connexon protein subunits comprise a hexagonal
connexion hemichannel in each cell membrane
Two hemichannels = gap junction channel

Gap junctions in Action

- Molecules that can diffuse through the gap
junction
o Ions, secondary messengers (cAMP,
calcium)
- Gap junctions allow rapid coordination of
cardiac muscle contraction and uterine
muscle contractions
- Hormonal stimulation of one
cell can lead to a response shared by many cells diffusion of
secondary messengers directly
o Ex. Fluorescent molecule injected into a single cell diffuses into
neighbouring cells joined by gap junctions
Plasmodesmata between Plant Cells
- Plasmodesmata: structures in plant cells that
have similar function to gap junctions
o Important to the structure and function
of phloem in flowering plants
Phloem: system of elongated tubes
formed from linear arrays of
connected cells. Carries nutrients
(products of photosynthesis- sucrose) from the leaves to the
rest of the plant
o Cells (sieve-tube elements) are connected by modified and
enlarged plasmodesmata which form the sieve tube plate
o Sieve tube elements are metabolically inactive, specialized cells
(companion cells) are closely associated with their development
and function
Companion cells provide ATP, proteins, and other
substances
Connected to phloem by plasmodesmata
o Spans the cell walls in addition to the cell membranes

Plasmodesmata in Action
- Phloem: circulatory system for the plant
 o Transports sucrose from source cells to the rest of the plant, as well
as informational macromolecules (transcription factors, gene
transcripts, small RNAs)
o Viral pathogens exploit these channels for intercellular spread

Anchoring Junctions
- Anchoring junctions: desmosomes, adherens
junctions, hemidesmosomes
o Distinguished from other junctions by
association with the cytoskeleton in particular
actin filaments
o Desmosomes: links two cells together
o Hemidesmosomes: attach one cell to the extracellular matrix
o Adherens junctions: connect the actin cytoskeleton between
neighbouring cells
Major Families of CAMs
- Cell adhesion molecules make up
adherens junctions fall into 4
families
1. Cadherins
2. Ig-superfamily
3. Integrins
4. Selectins
- Some are responsible for
association of similar cells
(hemophilic interactions)
others connect different cells
together (heterophilic
interactions)
Cassical Cadherins
- Critical cell adhesion molecules of the adherens junctions
- Ca2+ dependent CAMs hat mediate hemophilic interactions
- 3 major classes
1. E-cadherin (epithelial)
2. N-cadherin (neural)
3. P-cadherin (placental)
- Mediate epithelial cell-cell adhesion near the apical surface of the cells,
just below the tight junctions
- Adhesion is mediated by multiprotein complexes involving the
transmembrane cadherins, but also cytosolic cofactors (catenins) that
anchor cadherin to the actin skeleton
- Under standard cell culture conditions (with calcium) epithelial cells
do not aggregate into sheets
 o Introduce gene expressing E-
cadherin aggregation into
epithelial-like clumps
E-cadherin mediates Ca2+
dependent adhesion of
epithelial cells
Calcium adhesion
No calcium no adhesion

Cadherins and Cell Differentiation

- E-cadherin: mediates tissue-specific
adhesive connections in cultured
epithelial cells
- GFP: E-cadherin introduced into
cultured cells
o Mixed together in a calcium-
containing medium aggregation of E-cadherin expressing cells
o Accumulates at the surfaces of neighbouring cells cells adhere
only to other cells expressing the same cadherin = hemophilic
interactions