Cell Adhesion Flashcards
tight junction seals
gap between epithelial cells
adherent junction connects
actin filament bundle in one cell with that in the next cell
desmosomes connect
intermediate filaments in one cel to those in the next cell
gap junctions allow for the passage of
small water soluble molecules from cell to cell
actin linked cell matrix adhesion anchors
actin filaments in cell to extracellular matrix
hemidesmosome anchors
intermediate filaments in a cell to extracellular matrix
first principle of adhesion
cells define their capacity for adhesive interactions by selectively expressing plasma membrane receptors (cell adhesion molecules, aka: CAMs) with limited ligand-binding activity. Generally, expression of the proper mix of receptors is part of a genetic program for the differentiation of the cell. In some cases, extracellular stimuli control expression of adhesion receptors. For example, endothelial cells produce E-selectin only when stimulated by inflammatory hormones or endotoxin
second principle of adhesion
many adhesion proteins bind one main ligand, and many ligands bind a single type of receptor
if this one-to-one pairing were the rule, adhesion would be simple indeed. However, many exceptions exist, particularly in the
integrin family of receptors
these integrin receptors generally bind
more than one ligand, and some ligands, such as fibronectin, bind more than one integrin
Most cadherins prefer to bind
themselves
cadherins promote the adhesion of
like cells
homophilic interactions
association of like receptors on two cells
cadherin reactions require
ca
Selectins bind
anionic polysaccharides like those on mucins
Generally, such interactions bind together
two different types of cells
Most Ig-CAMs bind
other cell surface adhesion proteins
heterophilic interactions
association of unlike receptors on two cells
These heterophilic interactions may occur between
the same or different cell types
integrins stand apart because they bind
a variety of ligands
variety of ligands includes
matrix macromolecules, such as fibronectin and laminin; soluble proteins, such as fibrinogen in blood; and adhesion proteins on the surface of other cells, including Ig-CAMs and one cadherin
third principle of adhesion
Cells modulate adhesion by controlling the surface density, state of aggregation, and state of activation of their adhesion receptors
Surface density reflects not only the level of synthesis but also the
partitioning of adhesion molecules between the plasma membrane and intracellular storage compartments
endothelial cells express P-selectin constitutively but store it internally in membranes of cytoplasmic vesicles. When inflammatory cytokines activate endothelial cells, these vesicles
fuse with the plasma membrane, exposing P-selectin on the cell surface, where it binds white blood cells
cadherins control the
selective assortment of cells
cells can sort themselves out according to
the type and level of cadherins they express
cadherins
calcium-dependent adhesion molecules. Cadherins are critical for establishing and maintaining intercellular connections, and they appear to be crucial to the spatial segregation of cell types and to the organization of animal form (Takeichi 1987). Cadherins interact with other cadherins on adjacent cells, and they are anchored into the cell by a complex of proteins called catenins (Figure 3.31). The cadherin-catenin complex forms the classic adherens junctions that connect epithelial cells together. Moreover, since the catenins bind to the actin cytoskeleton of the cell, they integrate the epithelial cells together into a mechanical unit.
fourth principle of adhesion
The rates of ligand binding and dissociation are important determinants of cellular adhesion
Many cell surface adhesion proteins (including members of the Ig-CAM, cadherin, integrin, and selectin families) bind their ligands
weakly in comparison with other specific macromolecular interactions, such as the interaction of antigens and antibodies, hormones and receptors, or transcription factors and DNA
In some cases, this makes good biological sense. Rapidly reversible interactions allow white blood cells to
roll along the endothelium of blood vessels
Transient adhesion also allows fibroblasts to
migrate through connective tissue
On the other hand, the interactions of cells in epithelia and muscle appear to be more stable, perhaps owing to
multiple weak interactions between clustered adhesion proteins cooperating to stabilize adherens junctions and desmosomes
The combined strength of these bonds is said to increase the “—” of the interaction
avidity
fifth principle of adhesion
Many adhesion receptors interact with the cytoskeleton inside the cell
Adapter proteins link cadherins and integrins to (2)
actin filaments or intermediate filaments
These interactions provide mechanical continuity from cell to cell in muscles and epithelia, allowing them to t
ransmit forces and resist mechanical disruption
sixth principle of adhesion
Association of ligands with adhesion receptors can activate intracellular signal transduction pathways, leading to changes in gene expression, cellular differentiation, secretion, motility, receptor activation, and cell division
Signaling through adhesion receptors allows cells to
respond appropriately to physical interactions with the surrounding matrix or cells
Cells attach to the underlying extracellular matrix through two types of integrin-dependent junctions:
focal adhesions
hemidesmosomes
focal adhesions
attach the actin cytoskeleton to fibers of fibronectin
hemidesmosomes
connect intermediate filaments to basal laminae
Integrin-containing cell matrix junctions are found in (2)
highly motile cells such as skin keratinocytes, which are weakly adherent, and in immobile, strongly adherent cells such as epithelia
hemidesmosomes are found mainly on the
basal surface of epithelial cells
hemidesmosomes firmly anchor epithelial cells to the
underlying basal lamina
what does the cytosolic side of hemidesosomes consist of?
a plaque composed of adapter proteins, which are attached to the ends of keratin filaments
Integrin α6β4 is localized to
hemidesmosomes
Integrin α6β4 is thought to bind to
an adapter protein, plectin, within the plaques and to the extracellular-matrix protein laminin
by interconnecting the intermediate filaments of the cytoskeleton with the fibers of the basal lamina, these cell-matrix junctions increase the
overall rigidity of epithelial tissues
adhesion proteins play a role in (3)
platelet function
development
health/disease
E-cadherin (epithelial cadherin, also called uvomorulin and L-CAM) is expressed on
all early mammalian embryonic cells, even at the 1-cell stage
Later, this molecule is restricted to
epithelial tissues of embryos and adults
P-cadherin (placental cadherin) appears to be expressed primarily on the (2)
trophoblast cells (those placental cells of the mammalian embryo that contact the uterine wall) and on the uterine wall epithelium
It is possible that P-cadherin facilitates the connection of the
embryo to the uterus
since P-cadherin on the uterine cells is seen to contact P-cadherin on the trophoblast cells of mouse embryos
N-cadherin (neural cadherin) is first seen on
mesodermal cells in the gastrulating embryo as they lose their E-cadherin expression
N-cadherin is also highly expressed on the cells of the
developing central nervous system
EP-cadherin (C-cadherin) has been found to be critical for maintaining
adhesion between the blastomeres of the Xenopus blastula and is required for the normal movements of gastrulation
Protocadherins are calcium-dependent adhesion proteins that differ from the classic cadherins in that they
lack connections to the cytoskeleton through catenins
Protocadherins have been found to be very important in
separating the notochord from the other mesodermal tissues during Xenopus gastrulation
Cadherins join cells together by binding to the
same type of cadherin on another cell
cells with E-cadherin stick best to other cells with
E-cadherin, and they will sort out from cells containing N-cadherin in their membranes.
This pattern is called
Homophilic binding
how can cadherins be restricted in their expression?
spacially
what are the three functional roles of the basal lamina?
- molecular filter (retaining proteins in the blood while filtering toxic substances into the urine)
- cell barrier (ex. ameloblasts and odontoblasts separated by a basement membrane during tooth development)
- molecular scaffolding to aid in regeneration after injury
what do T cell use in the process of antigen presentation?
adhesion receptors
how are adhesion molecules used in antigen recognition?
colonel expansion
what process do cell adhesion receptors participate in?
sensation and response to mechanical forces
This transition to a motile state requires de-adhesion of cells from the extracellular matrix by (2)
inhibition of cell-matrix interactions
destruction of matrix components
One class of de-adhesion factors comprises small peptides, called
disintegrins
disintegrins contain the integrin-binding RGD sequence present in many
ECM proteins
By binding to integrins on the surface of cells, disintegrins competitively inhibit
binding of cells to matrix components
The disintegrins present in snake venoms, which prevent platelets from aggregating, are partly responsible for the
anticoagulant property of venoms
what does the second class of de-adhesion factors contains two types of proteases contain? (2)
ADAMs (ADAM-TS)
matrix-specific metalloproteinases (MMPs)
ADAMs
membrane bound proteases that catalyze shedding of transmembrane proteins
ADAM-TS
a soluble enzyme that cleaves non-fibrillary ECM proteins
By degrading ECM matrix components, these enzymes facilitate
cell migration
