LKB1 and SAD kinases define a pathway required for the polarization of cortical neurons.
The polarization of axon and dendrites underlies the ability of neurons to integrate and transmit information in the brain. We show here that the serine/threonine kinase LKB1, previously implicated in the establishment of epithelial polarity and control of cell growth, is required for axon specification during neuronal polarization in the mammalian cerebral cortex. LKB1 polarizing activity requires its association with the pseudokinase Stradalpha and phosphorylation by kinases such as PKA and p90RSK, which transduce neurite outgrowth-promoting cues. Once activated, LKB1 phosphorylates and thereby activates SAD-A and SAD-B kinases, which are also required for neuronal polarization in the cerebral cortex. SAD kinases, in turn, phosphorylate effectors such as microtubule-associated proteins that implement polarization. Thus, we provide evidence in vivo and in vitro for a multikinase pathway that links extracellular signals to the intracellular machinery required for axon specification.
Barnes
Anthony P
AP
Neuroscience Center, Department of Pharmacology, University of North Carolina, Chapel Hill, NC 27599, USA.
Lilley
Brendan N
BN
Pan
Y Albert
YA
Plummer
Lisa J
LJ
Powell
Ashton W
AW
Raines
Alexander N
AN
Sanes
Joshua R
JR
Polleux
Franck
F
D000818:Animals; D001369:Axons / Q000378:metabolism*; D002460:Cell Line; D045744:Cell Line, Tumor; D016764:Cell Polarity; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004622:Embryo, Mammalian / Q000166:cytology; D005260:Female; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008297:Male; D051379:Mice; D009474:Neurons / Q000166:cytology* / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D015398:Signal Transduction
C496826:Brsk1 protein, mouse; C496825:Brsk2 protein, mouse; D017346:Protein Serine-Threonine Kinases