Interactions Between Cells and

Their Environment
Week 5
Reading from Alberts
1131-1135, 1150-1155, 1158-1163,
1164-1168, 1178-1195
1

Cells are organised into tissues

Extracellular matrix =ECM

Figure 19-1 Molecular Biology of the Cell ( Garland Science 2008)

Epithelial Tissue

Connective Tissue

E.g. Intestinal lining, Skin

epidermis.

E.g. Bone, tendon

Cells closely associated

Cells are rarely connected

Limited ECM
(a thin basal lamina)

Plentiful ECM

Cytoskeletal filaments provide

resistance to mechanical
stress.

ECM provides resistance to

mechanical stress.

Cells are attached to:

Cells are attached to:

each other

the matrix

Different types of junctions between cells

link cell to cell or

cell to matrix

gap sealing

all present in epithelial cells

Figure 19-2 Molecular Biology of the Cell ( Garland Science 2008)

like synapses

In polarised epithelial cells:

Junctions are arranged in a specific order

common to almost
all epithelial
cells

Figure 19-3 Molecular Biology of the Cell ( Garland Science 2008)

not all cells have basal and apical

side, epithelial cells do

Tight Junctions
Create a tight seal between
cells:
Prevent mixing of the:
extracellular environments

Act as fences in the

membrane:
Prevent mixing of
membrane proteins
- Apical membrane proteins
- Basal membrane proteins

Figure 19-2b Molecular Biology of the Cell ( Garland Science 2008)

Epithelial sheets are a barrier

Figure 19-24 Molecular Biology of the Cell ( Garland Science 2008)

Claudin and Occludin proteins form the seal

Transmembrane proteins:
Extracellular domains
Interact with the extracellular
domains of the proteins in
the neighboring cell
Claudin/Claudin
Occludin/Occludin

Claudin:
required for tight junction
seals
Functional proteins are
required in both cells!

Figure 19-26b Molecular Biology of the Cell ( Garland Science 2008)

need proteins of both cells so they

can bind to each other

Several sealing strands wrap around the

perimeter of the cell creating a seal
Plasma membranes of
adjacent cells are
brought close together
at the sealing strand
Makes 3D seals
24 claudins in humans,
expressed in different
tissues,
create seals with different
permeability properties
Figure 19-26a Molecular Biology of the Cell ( Garland Science 2008)

Tight junctions are dependent on

adherens junctions
If you block the formation
of adherens junctions:
tight junctions dont
form properly

Junctional
complex

Desmoglein,
Desmocollin
Figure 19-27 Molecular Biology of the Cell ( Garland Science 2008)

tight junctions are

dependent on other
parts to form properly

Anchoring Junctions
adherens junctions and desmosomes are anchoring

Cell-cell anchoring
junctions

Cell-matrix anchoring
junctions
Link the cytoskeletons of
neighboring cells
Different proteins are
involved in different types
of interactions
Figure 19-2a Molecular Biology of the Cell ( Garland Science 2008)

Adhesion and anchor proteins link

cytoskeletal filaments of neighbouring cells
Adhesion proteins:

e.g. Cadherins
transmembrane proteins
The extracellular domains interact
with:
Adhesion proteins (neighbour)
Extracellular matrix
Intracellular domains interact with:
Anchor proteins

Anchor proteins:

Link the adhesion proteins to

cytoskeletal filaments
Cytosolic proteins

Figure 19-4 Molecular Biology of the Cell ( Garland Science 2008)

Adherens Junction
bundle of contractile actin filaments

The adhesion belt:

encircles the inside of
the plasma membrane

At adherens junctions:
Cadherin proteins from
neighbouring cells interact
Actin is tethered to
cadherin by anchor
proteins
N-terminal is outside
Figure 19-9c Molecular Biology of the Cell ( Garland Science 2008)
Figure 19-15 Molecular Biology of the Cell ( Garland Science 2008)

Desmosomes and Hemidesmosomes

Link intermediate filaments:
E.g. Keratin filaments
Intermediate filaments
provide the most structural
strength

Desmosome:
The link is to a neighboring cell

Hemidesmosome:
The link is to the basal lamina
(a special type of ECM)
Figure 19-18 Molecular Biology of the Cell ( Garland Science 2008)

Desmosome Structure
Specific cadherin family
members are the
adhesion proteins:
Desmoglein
Desmocollin

Anchor proteins link the

adhesion proteins to
intermediate filaments

Figure 19-17a Molecular Biology of the Cell ( Garland Science 2008)

Desmoglein, Desmocollin

Hemidesmosomes

Spot-weld epithelial cells to the

basal lamina
Keratin filaments
inside the cell

Linked to:

not directly linked, but linked together

laminin in the ECM.

Figure 19-46 Molecular Biology of the Cell ( Garland Science 2008)

In polarised epithelial cells:

Junctions are arranged in a specific order

Figure 19-3 Molecular Biology of the Cell ( Garland Science 2008)

Gap Junctions
Communication
between cells
Composed of:
Connexin proteins

Figure 19-2c Molecular Biology of the Cell ( Garland Science 2008)

Gap Junction Structure

Connexon
Hemichannel

Cytosol

Extracellular

Cytosol

Gap junction

connexon from one cell binds to other cell's cnxn

4 transmembrane domains per connexin protein

Cell Death and Differentiation (2009) 16, 524536.

Connexin

Gap junction Plaques

large means many channels

Figure 19-35 Molecular Biology of the Cell ( Garland Science 2008)

Different connexin proteins can be

present in the same channel
21 different kinds of connexins

affects selectivity
Figure 19-34b Molecular Biology of the Cell ( Garland Science 2008)

Gap junctions couple cells

Electrically and Metabolically
Allow the passage of:
Ions & Metabolites
< 1000 daltons

To test the permeability of a gap junction:

Passes through:
cAMP, nucleotides,
glucose, amino acids

Does not pass:

macromolecules
Proteins, nucleic acids
*not very selective as to what passes through the channel
Figure 19-33 Molecular Biology of the Cell ( Garland Science 2008)

Gap junctions are gated

Can be in an open or
closed state

CLOSED

One connexon on its own

(hemichannel) is usually:
Closed

A dramatic increase in
cytosolic Ca2+ will:
Close Gap junctions

OPEN

Gap junctions open

many things control opening/closing

Figure 19-37 Molecular Biology of the Cell ( Garland Science 2008)

Gap junctions closed

Gap junctional coupling of glial cells

Calcium transfer to adjacent cells through
gap junctions
Occurs in waves

http://www.dnatube.com/video/489/Cal
cium-Signaling

Gap junctions close in response to Ca2+

Cytosolic Ca2+ is usually low

Ca2+

Membrane damage:
Ca2+ leaks into the cell
Becomes abnormally high
Metabolites leak out

Gap junctions close:

In response to high Ca2+
to prevent losing metabolites
from adjacent cells

X
X

Basal Lamina
Special type of ECM
Underlies all epithelia
Thin (40-120 nm thick)
ECM is produced and
secreted by the cells in
the tissue
some components made by epithelial and connective
cells
Figure 19-39 Molecular Biology of the Cell ( Garland Science 2008)

The Basal Lamina of Epithelial Sheets

Figure 19-40 Molecular Biology of the Cell ( Garland Science 2008)

Basal lamina surrounds:

Muscle
Fat cells
Schwann cells
Structural role

In the kidney:
Divides two cell sheets
Acts as a selective filter

Can also influence cell

polarity
Figure 19-39 Molecular Biology of the Cell ( Garland Science 2008)

Laminin is thought to organise the basal lamina

Trimer of:
-laminin
-laminin
-laminin

Binds to:
Integrins (PM transmembrane proteins)
Many other components of the ECM
including:
Other laminin molecules

Figure 19-42a Molecular Biology of the Cell ( Garland Science 2008)

Hemidesmosome

Type IV collagen provides strength

The tails interact with
each other
Collagen IV forms a strong
flexible felt-like network
There are many proteinprotein interactions
between the different
components of the basal
lamina (and ECM)
Figure 19-43 Molecular Biology of the Cell ( Garland Science 2008)

laminin is first
Figure 19-43 Molecular Biology of the Cell ( Garland Science 2008)

The Basal Lamina:

cells, fibres, and ECM

fibroblasts are the cell types
in connective tissue

an attachment site for

epithelial cells.
prevents fibroblasts in the
underlying connective
tissue from interacting with
epithelial cells.
yet allows the passage of
macrophages and
lymphocytes.

fibroblasts have no apical/basal

Extracellular Matrix
Connective tissues:
E.g. bone, tendon

Different composition of ECM

Give tissues different properties

Not a static structure

Remodeled over time

Connective tissue underlying an epithelium

there are some sugars in ECM

Figure 19-53 Molecular Biology of the Cell ( Garland Science 2008)

Major components of the ECM

lots of glycoproteins
(sugars added to proteins)
Figure 19-41 Molecular Biology of the Cell ( Garland Science 2008)

Green = Protein components

Purple = Glycosaminoglycans

Glycosaminoglycans (GAGs)
Long, linear, polysaccharide chains composed of a
repeating disaccharide
Pair of sugars, one is an amino sugar
Highly negatively charged (attract Na+ and water)
Form a voluminous hydrated gel

green one is amino sugar

Figure 19-55 Molecular Biology of the Cell ( Garland Science 2008)

Hyaluronan
A simple GAG
Long chain of repeating
disaccharide subunits
(up to 25,000)
Not linked to a protein
Most GAG are synthesized
inside the cell on proteins and
exocytosed
But Hyaluronan is spun directly
from the cell surface by a
membrane protein complex
Figure 19-56 Molecular Biology of the Cell ( Garland Science 2008)

Proteoglycans vs Glycoproteins
proteoglycans are a subclass of
glycoproteins

Proteoglycans:
- at least one sugar side chain must be a GAG
- more extensive addition of sugars (up to 95% of total weight)
Proteoglycans of the ECM

Figure 19-59 Molecular Biology of the Cell ( Garland Science 2008)

Secreted Glycoprotein

Elastin gives Tissues Elasticity

Networks of elastin:
Stretch and relax like a
rubber band

Other components of
the ECM provide
strength preventing
the tissue from
excessive stretching
cross-links are covalent bonds
Figure 19-71 Molecular Biology of the Cell ( Garland Science 2008)

Interactions of cells with each other and with

the ECM are not simply structural
Classical sorting out experiment (1955)

Mix cells:
Mesoderm (green)
Neural plate (blue)
Epidermal (red)

cadherins form homotypic junctions

do not just bind with anything

Figure 19-10 Molecular Biology of the Cell ( Garland Science 2008)

Plant cell wall

Plant cells produce and
deposit their cell wall.
More rigid than the ECM
of animal tissues.
Composed of:
Cellulose
Pectin (polysaccharide)
cellulose: linear chain of hundreds to thousands of glucose units
Figure 19-76 Molecular Biology of the Cell ( Garland Science 2008)

Plasmodesmata; junctions between plant cells

Figure 19-38a,b Molecular Biology of the Cell ( Garland Science 2008)

From last week

I made a correction to the slide on actin
filament treadmilling. Please see the
following slide.
-actin filaments are composed of actin monomers

I added another slide on treadmilling.

Actin Filament Treadmilling

Although an actin filament looks stable

There is continual exchange of monomers at the

ends

Polymerisation is faster:

A pulse of
labelled actin
monomers

at the plus end

At the treadmilling concentration:

net loss of monomers at
the minus end

As this happens over time all the

monomers are eventually replaced
treadmilling
Panel 16-2 Molecular Biology of the Cell ( Garland Science 2008)

45

The plus end has a

higher affinity for actin
monomers than the
minus end

Steady-state
treadmilling
concentration of
monomers reached

End