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PHSL 233 > L12 (test 2) > Flashcards

L12 (test 2) Flashcards

1
Q

what is polarity

A

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

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2
Q

what does polarity mean in terms of epithelial cells

A

In epithelial cells this also means location of a

protein in a specific location (e.g. apical or basolateral) in the cellular membrane.

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3
Q

what is the first steep for a cell to become an epithelial cell

A

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

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4
Q

what 2 things are essential when establishing epithelial cell polarity

A

cell to basement membrane and cell to cell interactions

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5
Q

how do epithelial cells form the epithelium

A

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

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6
Q

after hemidesmosome formation, what is the next steep

A

steep 2 is the first cell to cell interaction through adherence junctions

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7
Q

what does the formation of adherence junctions initiate

A

epithelial formation

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8
Q

what if the main filament in adherence junctions

A

actin

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9
Q

what holds adherence junctions together

A

CAM

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10
Q

how do adherence junctions form

A
  1. Nectin proteins make initial cell to cell contact. Nectins on neighbouring cells interact. Ca2+-independent cell adhesion.
  2. E-cadherin on one cell forms homodimer with E-cadherin on neighbouring cell pulling the 2 cells tightly together, requires Ca2+.
  3. Cytoplasmic tail of E-cadherin binds catenins which links to the actin cytoskeleton.
  4. Catenins also link nectin and cadherin complexes to pull all the proteins together to make the AJ.
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11
Q

what is the role of nectin in adherence junction formation

A
  1. Nectin proteins make initial cell to cell contact. Nectins on neighbouring cells interact.

Ca2+-independent cell adhesion. doesn’t need Ca

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12
Q

what is the role of cadherin in adherence junction formation

A
  1. E-cadherin on one cell forms homodimer with E-cadherin on neighbouring cell pulling the 2 cells tightly together, requires Ca2+.
  2. Cytoplasmic tail of E-cadherin binds catenins which links to the actin cytoskeleton.
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13
Q

what is the role of Catenins in adherence junction formation

A
  1. Cytoplasmic tail of E-cadherin binds catenins which links to the actin cytoskeleton.
  2. Catenins also link nectin and cadherin complexes to pull all the proteins together to make the AJ.
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14
Q

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.

A

D

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15
Q

what is steep 3 in the formation of an epithelial cell

A

small GTP binding protein activation

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16
Q

what is steep 4 in the formation of an epithelial cell

A

activation of polarity complexes

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17
Q

how do GTP binding proetins get activated

A

the formation of AJ recruits many proetins. small GTP binding protein is one of these

18
Q

there are many small GTP binding proetins. we only have to remember the name of one of these. what is it

A

cdc42

19
Q

what/how do the polarity complexes get activated

A

steep 4 = activation of polarity complexes

cdc42 (GTP binding protein) activates protein kinase C (aPKC) which helps in the formation/activation of polarity complexes

20
Q

what are the 4 polarity complexes

A

aPKC, PAR, CRB, SCRIB

21
Q

what do the polarity complexes do

A

they maintain apical and basolateral polarity

one way they do this via the formations of tight junctions (steep 5)

22
Q

what do tight junctions interact with

A

apical polarity complexes

23
Q

what do tight junctions act as (3 roles)

A

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

24
Q

what happens is you remove ZO proteins from tight junctions

A

the cells will still maintain their polarity

25
Q

what is steep 5

A

the formation of tight junctions

26
Q

what is steep 6

A

positioning of 3 protein polarity complexes

27
Q

what are the 4 different polarity complexes in steep 6 and where are they located

A
  1. PAR complex – apical,
    near TJ
  2. CRB complex – apical,
    near TJ
  3. SCRIB complex –
    basolateral

the 4th one is aPKC

28
Q

what does the a stand for in aPKC

A

atypical

29
Q

what is aPKC activated by

A

small GTP binding proteins such as cdc42

30
Q

why is aPKC atypical

A

aPKC is the only polarity protein that
has enzymatic activity.

The other polarity proteins are ‘scaffolding’ proteins allowing clusters of
proteins to interact together.

31
Q

what does aPKC interact with/phosphorylate

A

CRB and SCRIB complexes

32
Q

what is mutual exclusion

A

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

33
Q

what are the 6 steeps of the formation of TJ and epithelial polarity

A
  1. Interactions between neighbouring cells, and between cells and basement
    membrane.
  2. Interaction between cells forms adherens junction.
  3. Small GTP proteins (cdc42) activated.
  4. Cdc42 activates aPKC - a polarity complex protein.
  5. Tight junctions start to form.
  6. Positioning of PAR and CRB polarity complexes to apical domain, and SCRIB
    complex to basolateral domain.

Apical-basolateral polarity established.

34
Q

Crumbs defines the basolateral domain and scribble defines the apical domain

BECAUSE

aPKC is the only polarity complex with
enzymatic activity

A

CRB is apical and SCRIB is basolateral

therefore the first statement is false and the second is true

35
Q

what happens to cause epithelial mesenchymal transition (the full process)

A

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)

36
Q

what does TGF beta DIRECTLY inhibit

A

It will directly inhibit the par complex which defines the apical domain.

37
Q

what happens when TGF beta activates SMADS

A

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
38
Q

what happens if they cells don’t reattach to the basement membrane

A

metastasis

39
Q

what do mutations in polarity complexes cause

A

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 )

40
Q

the cells divide when they sense that the epithelial layer is thinner/damaged. what sences this

A

ZO proteins

The ZO proteins will sense this and send transcription factors to the nucleus to stimulate cell division

41
Q

at high cell density what does ZO1 do

A

ZO1 keeps transcription factors that promote cell division localised to TJs
preventing cell division. Epithelia carries out regular functions e.g. absorption/secretion

42
Q

when do epithelial cells become cancerous

A

Genetic changes in cancer cells of epithelia may promote EMT: cell division increases and loss of
epithelial polarity.

PHSL 233 (31 decks)

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