Lecture 26 - Planar cell polarity

Question 1

What is it?

Answer 1

the coordinated polarization of cells within the plane of a tissue
- controls hair orientation

Question 2

What is a trichome?

Answer 2

a “hair”
- comes from a single cell
- all trichomes point in the same direction (proximal -> distal)

Question 3

What are the two main pathways that control PCP?

Answer 3

1. Core pathway
2. Ds-Ft pathway

• mutants have disorganized cell structures (e.g., trichomes)

Question 4

What are the 6 proteins that form asymmetrically localized intercellular complexes in the core pathway?

Answer 4

Distal complex:
1. frizzled (Fz): transmembrane
2. Dishevelled (Dsh): cytoplasmic
3. Diego (Dgo): cytoplasmic

Proximal complex:
4. Strabismus (Stbm) = Van Gogh: transmembrane
5. Prickle (Pk): cytoplasmic

Both sides:
6. Flamingo (Fmi) = starry night: transmembrane (both cells)
- a cadherin

Question 5

What is the minimal asymmetric complex?

Answer 5

the transmembrane proteins
- Fz, Fmi, Stbm

Question 6

How do the core proteins self-organize?

Answer 6

into mutually antagonistic sides
- cytoplasmic proteins mediate the positive and negative interactions
- non-cell autonomous effect: polarity propagates through the tissue

Question 7

How does PCP regulate trichome positioning?

Answer 7

via changes in actin cytoskeletal organization
- asymmetric localization of actin-binding proteins (i.e., concentrate actin-binding proteins to form hair structure)

Question 8

How do actin-binding proteins mediate trichome formation?

Answer 8

they restrict it to one side
- overall logic is to separate actin processes in the distal and proximal side
- some inhibit actin polymerization & others promote it
- mutants have many disoriented hairs

Question 9

Why is the Ft-Ds pathway called the global pathway?

Answer 9

because it aligns the entire tissue

Question 10

What are Ft and Ds? (what kind of proteins?)

Answer 10

they are cadherins that form heterophilic complexes with each other between adjacent cells
- they localize asymmetrically

Question 11

What drives the asymmetric localization of Ft and Ds?

Answer 11

the expression gradient of Fj (four jointed - a kinase) and Ds
- in the golgi, Fj phosphorylates extracellular cadherin repeats of Ft and Ds
- modifies Ft-Ds binding affinities
- promotes unfolding of binding domains on Ft

Question 12

What drives the asymmetric localization of the core proteins?

Answer 12

global cue => but not always

Question 13

Global pathway vs core pathway

Answer 13

global:
- converts expression gradient into small asymmetries
core:
- amplifies the small asymmetries into clear cellular structures