title: STRAD pseudokinases regulate axogenesis and LKB1 stability.
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) α and β. The roles of STRADα and STRADβ in the developing nervous system are not fully defined, nor is it known whether they serve distinct functions.
  
  
  RESULTS
  We find that STRADα 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 STRADα, whereby STRADα specifically maintains LKB1 protein levels via cytoplasmic compartmentalization.
  
  
  CONCLUSIONS
  We demonstrate a novel role for STRADβ in axogenesis and also show for the first time in vivo that STRADα, but not STRADβ, is responsible for LKB1 protein stability.
authors.forename: Biliana O
authors.initials: BO
authors.lastname: Veleva-Rotse
authors.forename: James L
authors.initials: JL
authors.lastname: Smart
authors.forename: Annette F
authors.initials: AF
authors.lastname: Baas
authors.forename: Benjamin
authors.initials: B
authors.lastname: Edmonds
authors.forename: Zi-ming
authors.initials: ZM
authors.lastname: Zhao
authors.forename: Allyson
authors.initials: A
authors.lastname: Brown
authors.forename: Lillian R
authors.initials: LR
authors.lastname: Klug
authors.forename: Kelly
authors.initials: K
authors.lastname: Hansen
authors.forename: Gabrielle
authors.initials: G
authors.lastname: Reilly
authors.forename: Alexandria P
authors.initials: AP
authors.lastname: Gardner
authors.forename: Krishnaveni
authors.initials: K
authors.lastname: Subbiah
authors.forename: Eric A
authors.initials: EA
authors.lastname: Gaucher
authors.forename: Hans
authors.initials: H
authors.lastname: Clevers
authors.affiliation: Department of Pediatrics-Doernbecher, Children's Hospital, Portland, OR 97239, USA. barnesan@ohsu.edu.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Barnes
mesh_terms: D055372:AMP-Activated Protein Kinases; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D001369:Axons / Q000378:metabolism / Q000502:physiology* / Q000648:ultrastructure; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D051379:Mice; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
chemical_list: D033942:Adaptor Proteins, Vesicular Transport; C518004:STRAD protein, mouse; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D055372:AMP-Activated Protein Kinases