On 2014 Sep 24, Jim Woodgett commented:

Interesting study and raises a number of questions. I wonder if MVB sequestration is a rescue/escape mechanism in cells to deal with constant signalling (since the initial studies used a constitutively active LRP6 variant)? I always wondered why so much (80+%) GSK-3 was reported to be sequestered when we could only ever find 5% of the entire cellular content of this kinase associated with Axin.

P.S. GSK-3alpha plays an equal role in Wnt signalling in mammals, although there is no equivalent in Drosophila. No small molecule inhibitor is able to discriminate between the GSK-3 isoforms (despite extensive literature).

On 2014 Sep 24, Jim Woodgett commented:

Interesting study and raises a number of questions. I wonder if MVB sequestration is a rescue/escape mechanism in cells to deal with constant signalling (since the initial studies used a constitutively active LRP6 variant)? I always wondered why so much (80+%) GSK-3 was reported to be sequestered when we could only ever find 5% of the entire cellular content of this kinase associated with Axin.

P.S. GSK-3alpha plays an equal role in Wnt signalling in mammals, although there is no equivalent in Drosophila. No small molecule inhibitor is able to discriminate between the GSK-3 isoforms (despite extensive literature).