Notesale: Turn your study into money

Document Preview

Extracts from the notes are below, to see the PDF you'll receive please use the links above

---

Notes on cell junctions - M
...
class lectures
Aman Bisht
June 27, 2023

Contents
1 The basic overview of cell junctions
...
1 Composition of multicellular organisms
...
1
...

1
...

1
...

1
...
1 Assembly of cells
...
3
...
1 What is cell polarity?
...
4 Cell Adhesion Molecules - CAMs
...


...


...


...



...


...


...


...


...


...


...



...


...


...


...


...


...


...



...


...


...


...


...


...


...



...


...


...


...


...


...


...



...


...


...


...


...


...


...



...


...


...


...


...


...


...



...


...


...


...


...


...


...



...


...


...


...


...


...


...


2 Cell junctions and their types
...
1 Types of cell junctions
...
2 Anchoring junctions
...
2
...

2
...

2
...
0
...

2
...
0
...

2
...
1 Catenins
...
3
...

2
...
3 Synaptic adhesion
...
4 Selectins
...
4
...
1 Selectin types and it’s binding mechanism
...
5 Desmosomes
...
6 Cells to extracellular matrix attachments
...
6
...

2
...

2
...

2
...
1 Functions of tight junctions
...
9 Caludins, Occludins, JAMs and Zona occludins
...
9
...

2
...
2 Occludins
...
9
...

2
...
4 JAMs
...
10 Gap junctions
...
10
...


2

3
3
3
3
3
3
4
4
5
5
5
6
6
7
8
9
9
10
11
11
12
13
13
13
14
15
15
15
15
15
15
16
16

Chapter 1

The basic overview of cell
junctions
...
1

Composition of multicellular organisms
...
These cells combine to from tissues
...

ˆ The extracellular matrix that supports the tissue and is made up of components produced by the cells present in the tissues
...
1
...


The extracellular matrix is a complex network of macromolecules like proteins, glycosaminoglycans, proteoglycans, etc
...

Specialized ECM include connective tissue, basal lamina, exoskeleton, cartilages and bones
...


1
...

These are present between two cells and hold two cells together
...

ˆ Extracellular matrix proteins
...


1
...


The arrangement of cells into tissues (and tissues into an organ) is highly complex and
sophisticated process
...
The organs are also compartmentalized and
behave in a highly regulated manner
...
3
...


When cells assemble into tissues:
ˆ They from a ordered and polar structure
...
These proteins are
involved in cell-cell adhesion and cell-matrix adhesion
...
3
...
1

What is cell polarity?

It is a state of orientation that is universally present (and necessary in tissues)
...
This ensures that the
basolateral surface is the surface that contacts others neighbouring cells and the extracellular
matrix
...
4

Cell Adhesion Molecules - CAMs
...
CAMs hae three domains:

ˆ An extracellular domain
...


ˆ Transmembrane region
...

The cytosolic domains of CAMs recuit a set of textbfadaptor proteins
...
They
can also recuit signalling molecules for signal transduction
...
A heterophilic interaction is when there
is interaction/attachment between two different CAMs
...
Some interactions are longlasting (example - nerve cells interacting with each
other) and some interactions are short lived (example - moving blood cells in a bloostream)
...
A trans interaction is when these dimers are used for interaction
between two different cells (or between cell and extra cellular matrix)
...
These are
intracellualr interactions
...
There are
intercellular interactions
...

2
...


There are four types of cell junctions:
ˆ Occluding junctions
...
They help seal cells together into sheets to
form an impermeable barrier
...

These are also called textbfgap junctions
...

ˆ Anchoring junctions
...
The attachment can either be between a cell and
a cell or between a cell and the extracellular matrix
...

These allow signals to be relayed from cell to cel across the plasma membrane
...
1: Types of cells junctions
...
2

Anchoring junctions
...
These junctions are connected to cell’s cytosol by their cytosolic domains
...
These adherent junctions are responsible for contact inhibition
...
2
...
1: Anchoring junctions based on anchoring proteins
...


Cell to Cell

These form desmosomes that are linked to intermediate filaments
...


Cell to Matrix

These form hemidesmosomes that are linked to intermediate filaments
...
2: Alternative tabular arrangement of Anchoring junctions
...


Desmosomes

Nonclassical
cadherins
(desmoglein
...


Cell-Matrix
Actin-linked cell
matrix junctions

Integrin

Extracellular
matrix proteins

Actin filaments

Talin, Kindlin,
Vanculin, Focal
adhesion kinase
etc
...
3

Cadherins
...
They are present in all multicellular organisms
...

ˆ N-cadherin
...

ˆ Non-classical cadherins
...
All cadherin proteins have an extracellular
portion containing extracellular cadherin domain that participates in Cadherin-Cadherin
binding
...
2: Structure of E-cadherin and N-cadherin
...
3
...
1

Cadherin to Cadherin binding
...

These end terminals are joined via a hinge
...


Figure 2
...
The presence of calcium (red dots) signifies
the so called hinge region
...
You can
observe that the presence of calcium provides rigidity to the structure by binding the the
hinge regions of the cadherin repeats
...
These interactions are

Figure 2
...

not non-selectively sticky
...
Cadherins allow
segregation of cells by selectively sticking similar cells together and excluding
other cells
...

2
...
0
...


In an experiment, some cells in culture were transfected with E cadherins and some cell
were transfected with N cadherin
...

Secondly, a similar setup was desinged with the exception that the cells were not transfected
with different cadherins but with the same cadherin expressed in different concentrations
...
This
indicated that cadherins help in cell sorting
...


(b) Cells expressing different
(a) Cells expressing two different types of
concentrations of cadherins - Higher
cadherin - N-cadherin(red) and
expression of E-cdherin(dark blue) and
E-cadherin(blue)
...


Figure 2
...


8

2
...
1

Catenins
...


Figure 2
...


2
...
2

Functions of cadherins
...

The Epithelial–Mesenchymal transitions depend on control of cadherins
...
On a similar note, same can happen to epithelial
cells
...

These transitions play a huge role in embryonic development and diseases like cancer
...

ˆ Mechanotransduction
...
In response to
the tension increase, the cell responds by strengthing it’s actin linkages
...
Under tension, the α-catenin unfolds and exposes a hidden domain
...


Figure 2
...

9

ˆ Tissue remodelling
...
The indirect linking of actins (by
cell-cell cadherin attachment) enable to tissues to use their actin cytoskeleton in a
coordinated way
...

In drosophila, soon after gastrulation, the outer epithelium goes an elongation process
called germ band extension
...
This whole process is actin dependent
(specifically actin dependent contraction called intercalation)
...


Figure 2
...


2
...
3

Synaptic adhesion
...
Thus the adhesive proteins like cadherins and other CAMs are situated at
the periphery, concentrated at specific spots
...

10

Figure 2
...
You can see that the proteins and
various receptors are attached to a scaffoding proteins that is then connected to actin
cytoskeleton
...
4

Selectins
...
One of the main roles in verterbrates is the
goberning the traffic of white blood cells during an inflammatory response
...

2
...
0
...


There are three types of selectins present on different types of cells
...

ˆ P-selectin - Present on platelets and on locally activated endothelial cells
...


The selectins have a conserved lectin domain that binds to a specific oligosaccharide on another cell
...
10: Structure of selectins
...
In lymphoid
organs, the endothelial cells express oligosaccharides (specific for L-selectin) and causes the
lymphocytes to be trapped
...

These selectins do not act alone but collabrate with integrins to strengthen the binding
(the binding between the selectins and the oligosaccharides are relatively weak)
...
5

Desmosomes
...
Their main function is to provide mechanical strength and are very
important in vertebrantes
...


Figure 2
...


Table 2
...

Type

Protein

Site of expression

Type I

Acidic keratines

Type II

Neutral and Basic keratins

Type III

Vimenin, Desmin etc

Presesnt in Muscle cells, glial cells, peripheral cells, etc
...
6

Cells to extracellular matrix attachments
...
There are two types of cell-ECM adhesions:
ˆ Focal adhesions
...


Figure 2
...


2
...
1

Functions of cell-matrix attachments

ˆ These help in ahdesion of cells to the basal substratum
...
Thus, they are crucial in cell motility, growth and survival
...
7

Integrins
...
Integrin dependent connections are strong and promote emigration
...
13: Selecting and Integrin mediated cell adhesion and emigration
...
Humans have 24 types of integrins present
...
14: Structure of integrins and their attachment to ECM
...
8

Occluding junctions/Tight junctions
...
They from a continious belt around the
circumference of the cell
...
The tight junctions
are composed of manily two proteins claudin and occludin
...
15: Tight junctions present in the cell
...
8
...


ˆ They limit the passage of molecules and ions through the space between cells
...

– In our digestive system, they prevent the digestive enzymes leaking into our blood
stream
...


– This ensures that endocytosis happens at the apical surface and the exocytosis
happens at the basolateral surface
...


2
...
9
...

Claudins
...
These are tetraspan proteins that have relatively short cytoplasmic tail (as compared to occludins)
...
The C-terminal of claudins usually ends in YV amino acid sequence
and is bound to PDZ domain of Zona occludins
...
9
...


These are also integral membrane proteins (60 kDa) that are involved in formation of tight
junctions
...
Similar to claudins, these proteins also form
two extracellular loop (and a cytosolic loop)
...

There are very few charged amino acids present
...


2
...
3

Zona occludins
...
(Special note: ZO-1
can associate themselves with Adhesion junctions in less polarized cells
...
Zona occludins link to actin cytoskeleton and belong to
MAGUK family of proteins (Membrane associated guanylate kinase proteins)
...
- These also mediate ineraction between claudins and Zona occludins
...
- These mediate protein interactions
...
- Guanlyl kinase domain that catalyses GDP to GMP
...
9
...


Thees belong to IgG superfamily (43 kDa glycosylated proteins)
...

There are four major types of JAMs:
15

Figure 2
...

ˆ JAM-1
...

ˆ JAM-2
...

ˆ JAM-3
...

ˆ JAM-4
...


Figure 2
...


2
...


Gap junctions allow exchange of electrical and chemical signals
...
The subunits of thse
channels are called connexins that assemble together to form connexons
...


2
...
1

Functions of gap junctions
...


16

(a) Connexins, Connexons and Gap
junctions
...


Figure 2
...

ˆ They are responsible for the action potential in heart rythmic contraction of
the heartbeat
...


17



---