Apical-basal polarity of epithelial cells?
Epithelial cells establish an apical-basal polarity which results from differential distribution of phsopholipids, protein complexes and cytoskeletal components between the various plasma membrane domains, reflecting their specialized functions.
What is apicobasal polarity dependent on?
Apicobasal polarity depends on the action of three protein complexes
What are the three protein complexes?
- Par complex
- Crumbs complex
- Scribble complex
What is intesreting about the three protein complexes?
Par, Scribble, and Crumbs are all mutually inhibitory, meaning that they are antagonists of one another and cannot exist mutually.
Where are these protein complexes found?
These in complexes are cytoplasmic.
Where are these complexes located?
The exact positions of these complexes vary slightly between tissues and species.
What do tight junctions act as?
Tight junctions (cadherins) act as ‘fences’ against transmembrane diffusion, locking the membrane asymmetry in place.
- They have different phospholipids and enzymes in the different domains, which cannot travel to other areas due to the nature of tight junctions
Antagonistic interactions between polarity factors do what?
Antagonistic interactions between polarity factors that maintain the identity and control the size of the apical, junctional and lateral domains.
- They are in the cytoplasm and also vry closely involved with the membrane.
what is aPKC?
aPKC is the main effector of apical identity bevcasue it phosphorylates the junctional and lateral polarity factors Par-3 and Lethal (2) giant larvae (Lgl) to exclude them from the apical domain.
What is the result of inhibiting Baz (Par-3)
Inhibiting Par-3 means that the binding to the cadherin is prevented
What is the result of inhibiitng Lgl?
Inhibited Lgl cannot associate with other in the complex when phosphorylated by aPKC
What does phosphoylation of Lgl do?
Phosphorylation of Lgl inhibits its association witht he other proteins in the complex.
aPKC and Lgl?
aPKC, a kinase, phosphoyrlates and inactivates Lgl
The scrib complex inhibits ____?
The Scrib complex inhibits aPKC
The three proteins are cytoplasmic, except what?
All the proteins re cytoplasmic except for Crumbs, which is located in the membrane.
Baz/Par-3?
Baz/Par-3 is a scaffold for cadherins, which then propagate the polarity in an epithelia so that all the cells are polarized equally
Crumbs is unique how?
Crumbs is the only transmembrane protein and links aPKC to the membrane (apical)
What happens withoiut functioning crumbs?
Without a functional crumbs complex, there is not an apical membrane
What happens if we lost apicobasal polarity?
Loss of apicobasal polarity leads to overproliferation and metastasis.
What is the EMT?
The epithelial-mesenchymal transition (EMT) is a process by which epithelial cells lose their cell polarity and cell-cel adhesion, and gain migratory and invasive properties.
History behind weird names of polarity genes?
- Cells in scribble complex mutants over proliferate
- lethal giant larvae was the first tumour suppressor gene
- tumour suppressors are genes that when mutated lead to uncontrolled proliferation
Imaginal disc?
An imaginal disc is a sac-like epithelial structure found inside the larvae of insects that undergo metamorphosis
- Ex. the eye owuld have its own disc that it is formed from
What happens to discs without apicobasal polarity?
Without apicobasal polarity, the discs overproliferate and form tumours
- AP polarity and caner are linked
Result of asymmetric division?
An asymmetric division produces two daughter cells with different cellular fates
- Orientation of the spindle determines fate and can lead to asymmetry in division.
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