The microtubule plus-end-tracking protein TACC3 promotes persistent axon outgrowth and mediates responses to axon guidance signals during development. Issue 1 (December 2017)

• Record Type: Journal Article
• Authors: Erdogan, Burcu; Cammarata, Garrett; Lee, Eric; Pratt, Benjamin; Francl, Andrew; Rutherford, Erin; Lowery, Laura
• Is Part Of: Neural development. Volume 12:Issue 1(2017)
• Page Start: 1
• Page End: 10
• Publication Date: 2017-12
• Subjects: Microtubule -- +TIPs -- TACC3 -- XMAP215 -- Xenopus laevis -- Neuronal development -- Growth cone -- Axon guidance; Neurology -- Periodicals; Nervous system -- Growth -- Periodicals; Developmental neurobiology -- Periodicals; 573.8
• DOI: 10.1186/s13064-017-0080-7
• Languages: English
• ISSNs: 1749-8104

Abstract

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 embryonicXenopus 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. Conclusion 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.