2 Matching Annotations
  1. Jul 2018
    1. On 2014 Aug 07, Jim Woodgett commented:

      Very thorough study on the effects of complete inactivation of GSK-3 (both isoforms) on radial migration of neurons and on dendritic morphology. The results here don't agree with previously reported role of Lkb1/STK11 on negative regulation of GSK-3 (via serine 21/9 phosphorylation). This is difficult to reconcile but may reflect the fact that such phosphorylation only partially inhibits GSK-3 (~50%) and that all compartments of GSK-3 are affected by genetic knockout verses only some that are sensitive to regulation by phosphorylation. The authors also show the effects of GSK-3 inactivation are not mediated by Wnt signalling which is typically the dominant pathway that is de-inhibited under this context and in, for example, nestin-Cre/GSK-3KO animals is one of the (but not only) primary drivers of neuronal progenitor proliferation. Together, the data indicate that the effects of these kinases on radial migration are largely insulated from the many other effects on cellular functions.

      As an aside, this paper makes great use of the embedded media of eLife although there is no direct link to the eLife manuscript from PubMed yet (http://elifesciences.org/content/3/e02663).


      This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.

  2. Feb 2018
    1. On 2014 Aug 07, Jim Woodgett commented:

      Very thorough study on the effects of complete inactivation of GSK-3 (both isoforms) on radial migration of neurons and on dendritic morphology. The results here don't agree with previously reported role of Lkb1/STK11 on negative regulation of GSK-3 (via serine 21/9 phosphorylation). This is difficult to reconcile but may reflect the fact that such phosphorylation only partially inhibits GSK-3 (~50%) and that all compartments of GSK-3 are affected by genetic knockout verses only some that are sensitive to regulation by phosphorylation. The authors also show the effects of GSK-3 inactivation are not mediated by Wnt signalling which is typically the dominant pathway that is de-inhibited under this context and in, for example, nestin-Cre/GSK-3KO animals is one of the (but not only) primary drivers of neuronal progenitor proliferation. Together, the data indicate that the effects of these kinases on radial migration are largely insulated from the many other effects on cellular functions.

      As an aside, this paper makes great use of the embedded media of eLife although there is no direct link to the eLife manuscript from PubMed yet (http://elifesciences.org/content/3/e02663).


      This comment, imported by Hypothesis from PubMed Commons, is licensed under CC BY.