From single cells
to complex multi-cellular organisms
Cell adhesion + Differentiation
N
ER
G
Lytic vacuole
Storage vacuole
Secretion
Mitochondria
Chloroplasts
Peroxisomes
Higher order structures on the outside of the cell:
Cell-adhesion tissue structures
Coordination of events within the cytosol and events
outside of the cell
Cell-cell adhesion needs to involve
membrane spanning proteins at the plasma membrane
Adhesion via
protein-protein
interactions
Problem: membranes are mostly liquids
Consequences:
Membrane spanning proteins alone do not
mediate adhesion.
Only the cytoskeleton of the cells can mediate
adhesion.
cytoskeleton --- cytoskeleton
cytoskeleton --- extracellular matrix
Cell-cell adhesion interfaces with the cytoskeleton
Desmosomes are buttonlike zones of intercellular contact,
they connect intermediate filaments of adjacent cells
Cell-cell adhesion interfaces with the actin cytoskeleton
Adhesion belts can shape parts of tissues
Anchoring junctions
Actin filament mediated
cell-cell or cell-matrix
Intermediate filament mediated
cell-cell or cell-matrix
Tight junctions prevent
diffusion of membrane spanning proteins and permit the
formation of membrane sub-domains
Cell adhesion and tight junctions can help
localising membrane proteins
Gap junctions serve to facilitate
exchange of small molecules between cells
Gap junctions are typically characterised by a
high concentration of protein channels
Proteins cannot pass, but small peptides, amino acids,
sugars, inorganic ions, nucleotides, ATP… can be exchanged.
Evidence for a role in electrical and chemical coupling
between cells
Plant Cells are connected by plasmodesmata(Comparison)
Cell-cell adhesion interfaces with the cytoskeleton
and the extracellular matrix
Integrins form a linkage between the extracellular matrix
and the cytoskeleton (regulatory or structural function)
Extracellular matrix:
Collagens
Fibronectins
Laminins
Cytoskeleton
(Actin)
Signalling
Example (structural): junctions that connect muscle cells to tendons
Collagen, an example of extracellular matrix components:
Fibroblast surrounded by collagen fibrils
Collagen biosynthesis occurs in the secretory pathway
Collagen assembly: composite materials
With sufficient overlap, many fibres act as one single fibre
Compare with glass-, kevlar-, or carbon fibre and composites
(windsurf boards, airplanes)
Elastins are important for tissue elasticity
Permits recoiling
Integrins form a linkage between the extracellular matrix
and the cytoskeleton
Extracellular matrix:
Collagens
Fibronectins
Laminins
Cytoskeleton
Signalling
SummaryIn multicellular organisms cells are linked to each other in many ways. We can
roughly split them in three major groups
Tight junctions prevent passive diffusion of membrane spanning proteins and help
create cell polarity. They are also called occluding junctions, because they are so
tight that not even small ions can pass through between two cells. This is important
in epithelia to create tight seals to contain fluids (blood stream, digestive fluids).
Desmosomes and adhesion belts are anchoring junctions to hold cells together by
linking the cytoskeleton of adjacent cells. Desmosomes connect intermediate
filaments of adjacent cells. Adhesion belts connect actin bundles of adjacent cells
and can play important roles in coordinated cell migration during development. These
junctions are formed by cadherins which are immunoglobulin-like membrane proteins
that bind to each other directly and to the cytoskeleton via specific adaptor protein
complexes. Another group of junctions uses integrins, which link the cytoskeleton of
cells to the extracellular matrix. This is relevant in tissues where cells are embedded
in a very large matrix and do not have any adjacent cells nearby.
Gap junctions are clusters of membrane spanning protein channels that are arranged
perfectly between two cell types to allow small molecules to pass from one cytosol to
That of the adjacent cell without crossinjg membranes. In plants this function is
carried out by the plasmodesmata, a completely different structure that relies on a
continuum between the plasma membrane and the ER of adjacent cells.
Signal-transductionHow signals are perceived and lead to
consequences in the cells
Intracellular signalling proteins
(molecular switches)
Receptor-ligand interaction
Intracellular consequencesDirect regulation of enzymes (modified biochemical reactions)
Altered gene expression (transcription factors)
Cytoskeleton + motor proteins (differences in cell shape)
Molecular switches and feedback
mechanisms
Not only in physics, also in Biology, every action
meets a countermeasure.
If a regulatory molecule is permanently turned on,
it would not work.
Permanently active signal transduction elements are
highly damaging and cause a lot of problems
(i.e cancer)
List of major signalling mechanisms
Low molecular weight GTPases (GEFs and GAPs)
Phosphorylated proteins (Kinases + phosphatases)
Secondary messengers:
cyclic AMP, cyclic GMP
cytosolic calcium levels
Target proteins sense these signals and change
shape, followed by modified actions, including
altered enzyme activity, altered ion-transport,
transcription, shapes and movements of organelles or
whole cells.
The general similarity of
signal transduction mechanisms
Phosphorylation
P
ATP
ADP
P
Incoming signal
GTP-binding proteins
GDPP
Incoming signal
GDP
GTP
GTP
Active state
Inactive state
onoff
onoff
Phosphorylation
P
ADP
ADP
P
Incoming signal
GDPP
Incoming signal
GDP
GDP
GDP
GTP-binding proteins
Active state
Inactive state
P
P
P
onoff
onoff
Let’s look at it in a different wayGTP and ATP are represented as GDP and ADP PP
Example: cell surface receptors
The EGF receptor binds to the EGF peptide and
transduces the signal to the cytosol via its cytosolic
tyrosine kinase activity
P P
EGF
EGF receptor
SOS(GEF)
P P
EGF
EGF receptor
SOS(GEF)
GDPP
GDP
GTP
GTP
Active state
Inactive state
onoff
RAS
RAS
Stimulated by
GAP
Example: cell surface receptors
The EGF receptor binds to the EGF peptide and
transduces the signal to the cytosol via its cytosolic
tyrosine kinase activity.
The GTPase RAS hands the signal over and starts
further signal transduction events, this time a
kinase cascade.
But when EGF continues to bind, then the EGF
receptor will be endocytosed via clathrin coated
vesicles and is digested in the lysosomes. This is
called “receptor down-regulation” (addictions).
Not all receptors are membrane
spanning
The transcription factor for the E.coli lac operon
can be regarded as a lactose receptor. When it
binds to lactose, it changes conformation and
looses its affinity to the operator, allowing the
RNA polymerase to transcribe the lac operon.
Certain hormones can pass biological membrane
and bind to intracellular receptors.
Receptors can bind to molecules, but can also
sense physicochemical parameters, such as
heat, cold and light.
Example of photo-reception:
Phytochrome
Conclusions:
Signalling cascades involve rapid and reversible
conformational shifts of proteins which can then
lead to further interactions with other proteins
that carry the signal further.
More than one pathway is usually employed to
downregulate the signal when the stimulus is
continuously present (i.e. GAP activity + receptor
endocytosis)
High energy phosphate bonds are the key to
switching between active and inactive states.
This principle is very conserved in nature.
Some examples of signals
Light of a certain wavelength
Low temperature (cold acclimation)
Polysaccharides released by plant pathogens
Hormones
Stress signals (salicyclic acid in plants)
Antigens of certain pathogens
Reading suggestions
Alberts et al:
Chapter 16 The cytoskeleton
Chapter 19 Cell junctions/adhesion..
Chapter 15 Cell communication
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