Fundamentals of Cell Biology
Chapter 6: The Extracellular
Matrix and Cell Junctions
iClicker Time
If cell biologists use the term “GTP cap” when discussing
microtubules, why don’t they use the term “ATP cap” when
discussing actin filaments?
A. ATP-bound actin monomers do not polymerize.
B. All actin monomers in an actin filament are bound to ATP.
C. Actin filaments do not undergo dynamic instability in cells.
D. Actin filament severing proteins cut the ATP cap off so quickly it
is usually not detectable.
E. Actin biologists don’t consider depolymerization of an actin
filament a catastrophe.
Chapter Summary: The Big Picture
(1)
• Chapter foci:
– Examine representative molecules that are
commonly found in the space between cells, the
extracellular matrix, which are highly specialized to
perform distinct functions in the extracellular spaces
and in cell–extracellular matrix junctions
– Examine the molecules that form direct links
between cells, cell–cell junctions, with an
introduction to several different kinds of cell–cell
junctions
Chapter Summary: The Big Picture (2)
• Section topics:
– The extracellular matrix is a complex network
of molecules that fills the spaces between
cells in a multicellular organism
– Cells adhere to one another via specialized
proteins and junctional complexes
The extracellular matrix (EM) is a complex
network of molecules that fills the spaces
between cells in a multicellular organism
• Key Concepts (1):
– The extracellular matrix is a dense network of
molecules that lies between cells in a multicellular
organism and is made by the cells within the
network.
– The principal function of collagen is to provide
structural support to tissues.
– The principal function of fibronectin is to connect
cells to matrices that contain fibrillar collagen.
– The principal function of elastin is to impart elasticity
to tissues.
The extracellular matrix (EM) is a complex
network of molecules that fills the spaces
between cells in a multicellular organism
• Key Concepts (2):
– The principal function of laminins is to provide an
adhesive substrate for cells and to resist tensile
forces in tissues.
– Proteoglycans consist of a central protein “core” to
which long, linear chains of disaccharides, called
glycosaminoglycans (GAGs), are attached.
The extracellular matrix (EM) is a complex
network of molecules that fills the spaces
between cells in a multicellular organism
• Key Concepts (3):
– The basal lamina is a thin sheet of EM found at the
basal surface of epithelial sheets and at
neuromuscular junctions and is composed of at
least two distinct layers.
– Cells express receptors for EM molecules. Virtually
all animal cells express integrins, which are the
most abundant and widely expressed class of EM
protein receptors.
Glycoproteins form filamentous
networks between cells
• Collagen provides
structural support to
tissues
 Basic unit: coiled
coil
 4 classes:Type I-IV
Figure 06.01: Collagen subunits are assembled into
triple-helical coiled coils.
Figure 06.02: Collagens are organized into four
major classes, which vary according to their
molecular formula, polymerized form, and tissue
distribution.
Structure of collagen fibers
• 3 polypeptide
subunits wrapped in
parallel to form a
300-nm-long coiled
coil
• characteristic repeat
sequence consisting
of glycine-X-Y
Figure 06.03: Schematic diagram
of collagen triple-helical coiled
coil (top), organization of coiled
coils within a fibril (middle), and
fibrils in a collagen fiber
(bottom).
Collagen assembly
Figure 06.04: Posttranslational modification and assembly of procollagen subunits.
Fibronectins connect cells to collagenous matrices
Figure 06.05: Two
fibronectin polypeptides
are covalently linked via
disulfide bonds near the
carboxyl terminus.
• fibronectin repeats
• classified into three
groups - Type I, II, III
• mechanism of fiber
assembly unclear but
believed that
fibronectin dimers
first bind to cell
surface receptors
called integrins
Figure 06.06: The fibronectin
dimer is secreted in a folded
conformation that is
stabilized by interactions
between fibronectin repeats
I1-5, III2-3 and III12-14.
Elastic fibers impart flexibility to tissues
• Elastin is
organized into
elastic fibers,
which consist of a
core region
enriched in
elastin proteins
surrounded by a
tough coating
called a
microfiber (or
microfibrillar)
sheath
Figure 06.08: Schematic representation of relaxed and
stretched elastic fibers.
Current model of elastin fibrilogenesis
Figure 06.09: Seven
steps of elastin fiber
assembly.
Laminins provide an adhesive substrate for cells
• 3 polypeptide
subunits
wrapped
together to
form a triple
helical coiled
coil
• each subunit
extends
“arms” out
from the coil
giving rise to a
cross-shaped
structure
Figure 06.10: The three chains of the laminin
molecules are wrapped into a central core.
Proteoglycans provide hydration to tissues
• provide tensile
strength
ensuring EM is
hydrated gel
• GAGs
• >40 different
core proteins
identified
• each contains
modular
structural
domains that
can bind to
components of
EM
Figure 06.12: Summary of proteoglycan structures.
Figure 06.15: Proteoglycans such
as aggrecan complex with collagen
II fibers in cartilage.
Hyaluronan is a GAG enriched in connective tissues
• binds to
proteoglycan
aggrecan
• creates
large,
hydrated
spaces in
the EM of
cartilage
Figure 06.15: Proteoglycans such as aggrecan
complex with collagen II fibers in cartilage.
The basal lamina is a specialized EM
• lies immediately
adjacent to, and
in contact with,
many cell types
• contains proteins
(collagen IV and
nidogen) found
only in this
structure
• adopts distinct,
sheet-like
arrangement
• “basement
membrane”
Figure 06.16: Hemisdesmosomes connect to the basement
membrane, which consists of the basal lamina and a network
of collagen fibers.
Figure 06.17: The basement
membrane. Caption A: The
basement membrane
appears as a thin layer of
protein immediately under
epithelial cells.
Most integrins are receptors for EM proteins
• bind to EM proteins
and membrane
proteins expressed
on surface of other
cells
• principal surface
proteins for holding
tissues together
• complex structure
• classified into 3
subfamilies based on
β subunits
Figure 06.18: Model of
integrin structure.
Figure 06.19: Integrins are
organized into subgroups that
share β subunits.
Specialized integrin clusters play distinct roles in cells
• clusters classified
into 5 types
• composition of
cluster varies
depending on
type(s) of integrins
in cluster, type of
EM bound by
integrins, degree of
tensile strain
imposed on cluster,
location of cluster
in cell, and type of
cell in which cluster
forms
Figure 06.21: Five types of integrin clusters.
Filopodia
Figure 05.35: Different forms of actin in stationary and migrating cells.
Integrins control a vast range of cellular functions
Figure 06.23: Summary of integrin cluster components and the cellular activities they control.
Hemidesmosomes
• contain α6β4
integrin and link
to the IF network
• cell surface
junction found at
basal surface of
plasma
membrane of
epithelial cells
The Module
• What you need to know:
– What epidermolysis bullosa is, and what causes it
– What the Central Dogma of Molecular Biology is, and
how EB demonstrates it.
– The difference between a hypothesis and a guess
– The structure of a logical argument
– How the data in the first research article (Module 1-2)
contribute to our understanding of EB
– How the data in Figure 1 of the second research article
(Module 1-3) were generated, and what they reveal
about the cause of EB.
iClicker Time
What structural property makes proteoglycans
distinct from all other extracellular matrix
molecules?
A. They are polar and thus bind to water.
B. They are not found in basement membranes.
C. They contain no amino acids.
D. They do not bind to any other cellular molecules.
E. Their function is determined largely by the sugars
they contain.
Cells adhere to one another via
specialized proteins and junctional
complexes
• Key Concepts (1):
– Cell–cell junctions are specialized protein complexes
that allow neighboring cells to adhere to and
communicate with one another.
– Tight junctions regulate transport of particles between
epithelial cells and preserve epithelial cell polarity by
serving as a “fence” that prevents diffusion of plasma
membrane proteins between the apical and basal
regions.
– Adherens junctions are a family of related cell-surface
domains that link neighboring cells together.
Cells adhere to one another via
specialized proteins and junctional
complexes
• Key Concepts (2):
– The principal function of desmosomes is to provide
structural integrity to sheets of epithelial cells by
linking the IF networks of cells.
– Hemidesmosomes are found on the basal surface of
epithelial cells, where they link the EM to the IF
network via transmembrane receptors.
– Gap junctions are protein structures that facilitate
direct transfer of small molecules between adjacent
cells. They are found in most animal cells.
Cells adhere to one another via specialized
proteins and junctional complexes
• Key Concepts (3):
– Cadherins constitute a family of cell surface
transmembrane receptor proteins that are
organized into eight groups. The best-known
group of cadherins, called classical cadherins,
plays a role in establishing and maintaining
cell–cell adhesion complexes such as the
adherens junctions.
Cells adhere to one another via specialized
proteins and junctional complexes
• Key Concepts (4):
– Neural cell adhesion molecules (NCAMs) are
expressed only in neural cells and function
primarily as homotypic cell–cell adhesion and
signaling receptors.
– Selections are cell–cell adhesion receptors
expressed exclusively on cells in the
circulatory system. They arrest circulating
immune cells in blood vessels so that they
can crawl out into the surrounding tissue.
Tight junctions form selectively permeable barriers
between cells
• junctional
complex is made
up of:
– tight junction
– adherens
junction
– desmosome
Figure 06.25: The junctional
complex is composed of at least
three distinct cell-cell junctions.
Tight junctions
• 3 types of
transmembrane
proteins found in the
tight junction:
claudins, occludins,
and the junctional
adhesion molecule
(JAM)
• functions as a
permeability barrier
Figure 06.27: Tight
junctions are held
together by occludin,
claudin, and junctional
adhesion molecules.
Figure 06.28: A model of
fast and slow transport of
solutes through tight
junctions.
Adherens junction
• hold epithelial and
endothelial cells
together – resist stress
• zonula adherens
• adhesive junctions in
synapses
• intercalated disks
between adjacent
cardiac muscle cells
• junctions between
layers of myelin sheath
Figure 06.30: The
zonula adherens is
part of the junctional
complex.
Figure 06.31: Each
type of adherens
junction functions to
hold adjacent cells
together tightly.
Desmosome
• thick accumulations of
fibrils running across gap
between two plasma
membranes of epithelial
cells
• fibrils terminate in electrondense material on
cytosolic side of plasma
membrane
• electron-dense patches
are connected to filaments
in cytosol of each cell
Figure 06.33: Desmosome proteins are
distributed in the plasma membrane
and a distinctive double plaque
arrangement at the cell surface.
Gap junctions allow direct transfer of
molecules between adjacent cells
• cell-to-cell transport of
ions and small
molecules
• connexons
– 6 connexin
subunits
Figure 06.34: The
principal structural unit
of the gap junction is the
connexon, which consists
of six membranespanning connexin
subunits.
Calcium-dependent cadherins mediate adhesion between cells
• 70 structurally-related
transmembrane proteins
• 2 properties:
– 1) bind to calcium ions to
fold properly (Ca, for
calcium)
– 2) adhere to other
proteins (adherin)
Figure 06.37: Cadherin cytoplasmic tails are linked to actin filaments
via catenin proteins.
Figure 06.38: As the neural tube is formed, the apical surface of
the neural plate cells constricts, causing the neural plate to curve
inward.
Calcium-independent NCAMs mediate
adhesion between neural cells
Figure 06.39: NCAMs are produced as
both membrane-bound and soluble
proteins of different sizes.
Figure 06.40: Strong and weak cellcell adhesion.
Selectins control adhesion of circulating
immune cells
Figure 06.41: An illustration of the “rolling stop”
function of selectins.