Abstract
Background: Neuronal polarization is an essential step of morphogenesis and connectivity in the developing brain. The serine/threonine kinase LKB1 is a key regulator of cell polarity, metabolism, tumorigenesis, and is required for axon formation. It is allosterically regulated by two related and evolutionarily conserved pseudokinases, STe20-Related ADapters (STRADs) alpha and beta. The roles of STRAD alpha and STRAD beta in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions. Results: We find that STRAD alpha is highly spliced and appears to be the primal STRAD paralog. We report that each STRAD is sufficient for axogenesis and promoting cell survival in the developing cortex. We also reveal a reciprocal protein-stabilizing relationship in vivo between LKB1 and STRAD alpha, whereby STRAD alpha specifically maintains LKB1 protein levels via cytoplasmic compartmentalization. Conclusions: We demonstrate a novel role for STRAD beta in axogenesis and also show for the first time in vivo that STRAD alpha, but not STRAD beta, is responsible for LKB1 protein stability
Translated title of the contribution | STRAD pseudokinases regulate axogenesis and LKB1 stability |
---|---|
Original language | Undefined/Unknown |
Article number | 5 |
Pages (from-to) | 5 |
Number of pages | 1 |
Journal | Neural development [E] |
Volume | 9 |
Publication status | Published - 2014 |