title: GSK3 regulates mitotic chromosomal alignment through CRMP4.
abstract: BACKGROUND
  Glycogen Synthase Kinase 3 (GSK3) has been implicated in regulating chromosomal alignment and mitotic progression but the physiological substrates mediating these GSK3-dependent effects have not been identified. Collapsin Response Mediator Protein 4 (CRMP4) is a cytosolic phosphoprotein known to regulate cytoskeletal dynamics and is a known physiological substrate of GSK3. In this study, we investigate the role of CRMP4 during mitosis.
  
  
  RESULTS
  Here we demonstrate that during mitosis CRMP4 phosphorylation is regulated in a GSK3-dependent manner. We show that CRMP4 localizes to spindle microtubules during mitosis and loss of CRMP4 disrupts chromosomal alignment and mitotic progression. The effect of CRMP4 on chromosomal alignment is dependent on phosphorylation by GSK3 identifying CRMP4 as a critical GSK3 substrate during mitotic progression. We also provide mechanistic data demonstrating that CRMP4 regulates spindle microtubules consistent with its known role in the regulation of the microtubule cytoskeleton.
  
  
  CONCLUSIONS
  Our findings identify CRMP4 as a key physiological substrate of GSK3 in regulating chromosomal alignment and mitotic progression through its effect on spindle microtubules.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, Montreal, Quebec, Canada.
authors.forename: Stephan
authors.initials: S
authors.lastname: Ong Tone
authors.forename: Bama
authors.initials: B
authors.lastname: Dayanandan
authors.forename: Alyson E
authors.initials: AE
authors.lastname: Fournier
authors.forename: Craig A
authors.initials: CA
authors.lastname: Mandato
mesh_terms: D002875:Chromosomes / Q000648:ultrastructure*; D003599:Cytoskeleton / Q000378:metabolism; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis; D009124:Muscle Proteins / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D010957:Plasmids / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D008941:Spindle Apparatus / Q000378:metabolism
chemical_list: C102926:DPYSL3 protein, human; D009124:Muscle Proteins; D034741:RNA, Small Interfering; D038362:Glycogen Synthase Kinase 3