Acute inactivation of the serine-threonine kinase Stk25 disrupts neuronal migration.
BACKGROUND
Neuronal migration involves the directional migration of immature neurons. During much of the migration period these neurons are polarized with defined leading and trailing processes. Stk25 has been shown to bind to the LKB1 activator STRAD and regulate neuronal polarization and dendritogenesis in an opposing manner to Reelin-Dab1 signaling. It is not known, however, whether Stk25 controls neuronal migration, a key developmental process regulated by Reelin-Dab1 signal transduction.


RESULTS
Here we find that while constitutive Stk25 deficiency does not lead to neuronal phenotypes, acute reduction by either Cre-mediated gene inactivation or by knockdown causes a developmental neuronal migration error. Furthermore, we find that knockdown of LKB1, STRAD and GM130, molecules that have previously been implicated with Stk25, causes similar aberrations in neuronal migration.


CONCLUSIONS
Loss of Stk25 function early in development likely leads to functional compensation for its roles in neuronal development. Stk25 regulates neuronal positioning, possibly as part of the LKB1-STRAD-Stk25-GM130 pathway that was previously shown to be important for neuronal polarization.
Tohru
T
Matsuki
Jianhua
J
Chen
Department of Neuroscience and Physiology, SUNY Upstate Medical University, 750 E, Adams St, Syracuse, NY 13210, USA. howellb@upstate.edu.
Brian W
BW
Howell
D000818:Animals; D001921:Brain / Q000196:embryology*; D002465:Cell Movement; D015870:Gene Expression; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D000091042:Reelin Protein; D000099317:Hippo Kinases
D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D000091042:Reelin Protein; C530661:Stk25 protein, mouse; D000099317:Hippo Kinases; C000717128:Reln protein, mouse