Notch & Wnt

Question 1

What happens when delta binds notch?

Answer 1

S2 cleavage by ADAM, releasing extracellular domain,
S3 cleavage by gamma-secretase releasing NCID
NCID translocates to nucleus
Interacts with Su-H - transcription activated.

Question 2

What Is the final stage of lateral inhibition?

Answer 2

one cell expresses high delta, inducing high notch in neighbouring cell.
negative feedback results in high notch cell expressing no delta so can’t activate notch in neighbouring cell.

Question 3

what experiments are done with notch?

Answer 3

knock out notch,
with gamma-secretase inhibitor
structure of epithelia maintained but all cells become secretory.

Question 4

ehat experiments are performed with DKK1?

Answer 4

forced expression inhibits Wnt –> loss of crypts & decrease in villus size in mice

over-expression blocks Wnt –> absorptive cells differentiate but secretory lost.

Question 5

what does B-catenin complex with in the absence of Wnt?

what is notable about it?

Answer 5

axin, APC, a kinase & GSK3.

unconventional NLS.

Question 6

what happens after Wnt binds frizzled & LRP?

Answer 6

LRP cytosolic domain phosphorylated 
axon binds cytosolic LRP domain
complex disrupted 
B-catenin freed. 
TCF (groucho displaced)