Lecture 25 - Apical-basal polarity Flashcards
How do epithelial cells establish AB polarity?
from differential distribution of phospholipids, protein complexes, and cytoskeletal components between the various plasma membrane domains
AB polarity depends on the action of what 3 protein complexes?
- Par complex
- Crumbs complex
- Scribble complex
The 3 protein complexes are mutually _______
inhibitory
- inhibit each other; lots of one complex in one area of cell, but not in another
What do junctions (cadherins) do?
they act as fences against transmembrane diffusion => lock asymmetry in place
What maintains the identity and controls the size of the apical, junctional and lateral domains?
antagonistic interactions between polarity factors
aPKC
the main effector of apical identity
- phosphorylates the junctional and lateral polarity factors Par-3 and Lethal (2) giant larvae (Lgl) to exclude them from the apical domain
What does the phosphorylation of Lgl do?
it inhibits the association of LgL with the other proteins in the complex
- Lgl cannot join the Scrib complex
What inhibits aPKC?
the Scrib complex (i.e., when Lgl is able to join the complex, it inhibits the kinase that will inhibit Lgl form joining Scrib
What protein is not cytoplasmic?
Crumbs => associates to membrane
** important because one of the complexes must know where to go to start the polarity, otherwise they’ll all go wherever and there won’t be the right polarity
How is the polarity propagated from cell to cell?
Crumbs knows what a membrane is, starts polarity in that cell
Baz/Par-3 is a scaffold for cadherins => cadherins then propagate the polarity of that cell to other cells, ensuring polarity is equal across all cells
Crumbs links aPKC to the membrane, why is this important?
otherwise aPKC will phosphorylate protein all over the cell => no polarity, cells no longer know whats up and whats down => will not organize properly
Loss of AB polarity leads to?
overproliferation and metastasis
- most cancers are caused from loss of AB polarity
Imaginal disc
a sac-like epithelial structure found inside the larva of insects that undergo metamorphosis
What happens to the imaginal disc if there is no AB polarity?
they overproliferate and form tumours
