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