title: The microtubule plus-end-tracking protein TACC3 promotes persistent axon outgrowth and mediates responses to axon guidance signals during development.
abstract: BACKGROUND
  Formation of precise neuronal connections requires proper axon guidance. Microtubules (MTs) of the growth cone provide a critical driving force during navigation of the growing ends of axons. Pioneer MTs and their plus-end tracking proteins (+TIPs) are thought to play integrative roles during this navigation. TACC3 is a + TIP that we have previously implicated in regulating MT dynamics within axons. However, the role of TACC3 in axon guidance has not been previously explored.
  
  
  RESULTS
  Here, we show that TACC3 is required to promote persistent axon outgrowth and prevent spontaneous axon retractions in embryonic Xenopus laevis neurons. We also show that overexpressing TACC3 can counteract the depolymerizing effect of low doses of nocodazole, and that TACC3 interacts with MT polymerase XMAP215 to promote axon outgrowth. Moreover, we demonstrate that manipulation of TACC3 levels interferes with the growth cone response to the axon guidance cue Slit2 ex vivo, and that ablation of TACC3 causes pathfinding defects in axons of developing spinal neurons in vivo.
  
  
  CONCLUSIONS
  Together, our results suggest that by mediating MT dynamics, the + TIP TACC3 is involved in axon outgrowth and pathfinding decisions of neurons during embryonic development.
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Burcu
authors.initials: B
authors.lastname: Erdogan
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Garrett M
authors.initials: GM
authors.lastname: Cammarata
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Eric J
authors.initials: EJ
authors.lastname: Lee
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Benjamin C
authors.initials: BC
authors.lastname: Pratt
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Francl
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA.
authors.forename: Erin L
authors.initials: EL
authors.lastname: Rutherford
authors.affiliation: Department of Biology, Boston College, Chestnut Hill, MA, 02467, USA. Laura.lowery@bc.edu.
authors.forename: Laura Anne
authors.initials: LA
authors.lastname: Lowery
mesh_terms: D000818:Animals; D000071437:Axon Guidance; D020439:Growth Cones / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000502:physiology; D008870:Microtubules / Q000502:physiology; D000071446:Neuronal Outgrowth; D058105:Polymerization; D014157:Transcription Factors / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis
chemical_list: C486738:CKAP5 protein, Xenopus; D008869:Microtubule-Associated Proteins; C474872:TACC3 protein, Xenopus; D014157:Transcription Factors; D029867:Xenopus Proteins
keywords: +TIPs; Axon guidance; Growth cone; Microtubule; Neuronal development; TACC3; XMAP215; Xenopus laevis