L12 (test 2) Flashcards
what is polarity
A difference in structure, composition or function between the two poles of a cell, such as apical/basolateral in an epithelial cell, axon/dendrites in a neuron
what does polarity mean in terms of epithelial cells
In epithelial cells this also means location of a
protein in a specific location (e.g. apical or basolateral) in the cellular membrane.
what is the first steep for a cell to become an epithelial cell
when the cell is first formed the protein channels will be scattered randomly (it has not apical and basolateral side)
the first thing that happens is the cell will bind to the basal laminar via hemidesmosomes to help ordinate the cell
what 2 things are essential when establishing epithelial cell polarity
cell to basement membrane and cell to cell interactions
how do epithelial cells form the epithelium
the founder cell (which is like a stem cell) divides when you get a scratch of something
the new cells will then form connections with the basal laminar through hemidesmosomes
then the new cell will form intercellular connections with neighboring epithelial cells helping to form an enlarged epithelium
after hemidesmosome formation, what is the next steep
steep 2 is the first cell to cell interaction through adherence junctions
what does the formation of adherence junctions initiate
epithelial formation
what if the main filament in adherence junctions
actin
what holds adherence junctions together
CAM
how do adherence junctions form
- Nectin proteins make initial cell to cell contact. Nectins on neighbouring cells interact. Ca2+-independent cell adhesion.
- E-cadherin on one cell forms homodimer with E-cadherin on neighbouring cell pulling the 2 cells tightly together, requires Ca2+.
- Cytoplasmic tail of E-cadherin binds catenins which links to the actin cytoskeleton.
- Catenins also link nectin and cadherin complexes to pull all the proteins together to make the AJ.
what is the role of nectin in adherence junction formation
- Nectin proteins make initial cell to cell contact. Nectins on neighbouring cells interact.
Ca2+-independent cell adhesion. doesn’t need Ca
what is the role of cadherin in adherence junction formation
- E-cadherin on one cell forms homodimer with E-cadherin on neighbouring cell pulling the 2 cells tightly together, requires Ca2+.
- Cytoplasmic tail of E-cadherin binds catenins which links to the actin cytoskeleton.
what is the role of Catenins in adherence junction formation
- Cytoplasmic tail of E-cadherin binds catenins which links to the actin cytoskeleton.
- Catenins also link nectin and cadherin complexes to pull all the proteins together to make the AJ.
Which processes are required for establishing epithelial polarity?
A. Neighbouring cells interacting with each other through
adherens junctions.
B. Connections between epithelial cells and their basement membrane.
C. Nectin proteins from neighbouring cells connecting with each other.
D. All of the above.
D
what is steep 3 in the formation of an epithelial cell
small GTP binding protein activation
what is steep 4 in the formation of an epithelial cell
activation of polarity complexes
how do GTP binding proetins get activated
the formation of AJ recruits many proetins. small GTP binding protein is one of these
there are many small GTP binding proetins. we only have to remember the name of one of these. what is it
cdc42
what/how do the polarity complexes get activated
steep 4 = activation of polarity complexes
cdc42 (GTP binding protein) activates protein kinase C (aPKC) which helps in the formation/activation of polarity complexes
what are the 4 polarity complexes
aPKC, PAR, CRB, SCRIB
what do the polarity complexes do
they maintain apical and basolateral polarity
one way they do this via the formations of tight junctions (steep 5)
what do tight junctions interact with
apical polarity complexes
what do tight junctions act as (3 roles)
Barrier: limits passage of ions and molecules between cells in the paracellular pathway.
Gate: can allow certain solutes to flow through the paracellular pathway.
Fence: prevent movement of proteins between apical and basolateral domains
what happens is you remove ZO proteins from tight junctions
the cells will still maintain their polarity
what is steep 5
the formation of tight junctions
what is steep 6
positioning of 3 protein polarity complexes
what are the 4 different polarity complexes in steep 6 and where are they located
- PAR complex – apical,
near TJ - CRB complex – apical,
near TJ - SCRIB complex –
basolateral
the 4th one is aPKC
what does the a stand for in aPKC
atypical
what is aPKC activated by
small GTP binding proteins such as cdc42
why is aPKC atypical
aPKC is the only polarity protein that
has enzymatic activity.
The other polarity proteins are ‘scaffolding’ proteins allowing clusters of
proteins to interact together.
what does aPKC interact with/phosphorylate
CRB and SCRIB complexes
what is mutual exclusion
When phosphorylated the polarity complexes are correctly located in
their apical or basolateral domain.
therefore when CRB and SCRIB are phosphorylated they stop moving as they are phosphorylated when they are in their correct location
what are the 6 steeps of the formation of TJ and epithelial polarity
- Interactions between neighbouring cells, and between cells and basement
membrane. - Interaction between cells forms adherens junction.
- Small GTP proteins (cdc42) activated.
- Cdc42 activates aPKC - a polarity complex protein.
- Tight junctions start to form.
- Positioning of PAR and CRB polarity complexes to apical domain, and SCRIB
complex to basolateral domain.
Apical-basolateral polarity established.
Crumbs defines the basolateral domain and scribble defines the apical domain
BECAUSE
aPKC is the only polarity complex with
enzymatic activity
CRB is apical and SCRIB is basolateral
therefore the first statement is false and the second is true
what happens to cause epithelial mesenchymal transition (the full process)
when we get a scratch cells need to divide therefore the polarity complexes have to be pulled apart for cell division, then they are reformed, so have to be able to change rapidly
this happens when TGF-beta binds to its receptor which leads to the disruption of tight junctions, adherens junctions and polarity complexes in 1 of 2 ways
It will directly inhibit the par complex which defines the apical domain.
It also will activate proteins called SMADS which when activated translocated into the nucleus.
SMADS are transcription facts which lead to an increased expression on snail, zeba and twist. These proteins will downregulate proteins that are important in tight and adherence junction formation.
EG snail zeb and twist downregulate
- Cadherence - Claudinds - Acculdends - ZO proetins
Without these we don’t have tight and adherence junction therefore they fall apart (even coming off the basement membrane)
what does TGF beta DIRECTLY inhibit
It will directly inhibit the par complex which defines the apical domain.
what happens when TGF beta activates SMADS
when activated translocated into the nucleus.
SMADS are transcription facts which lead to an increased expression on snail, zeba and twist. These proteins will downregulate proteins that are important in tight and adherence junction formation.
EG snail zeb and twist downregulate
- Cadherence - Claudins - Occludins - ZO proteins
what happens if they cells don’t reattach to the basement membrane
metastasis
what do mutations in polarity complexes cause
Decreased formation or lack of tight junctions so barrier, gate and fence functions compromised.
Changes in cell-cell adhesion and cell movement.
Changes in location of apical and basolateral proteins.
Cancer (A number of these polarity complexes have been seen to be tumor suppressors )
the cells divide when they sense that the epithelial layer is thinner/damaged. what sences this
ZO proteins
The ZO proteins will sense this and send transcription factors to the nucleus to stimulate cell division
at high cell density what does ZO1 do
ZO1 keeps transcription factors that promote cell division localised to TJs
preventing cell division. Epithelia carries out regular functions e.g. absorption/secretion
when do epithelial cells become cancerous
Genetic changes in cancer cells of epithelia may promote EMT: cell division increases and loss of
epithelial polarity.
