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XB-ART-53114
Neural Dev February 15, 2017; 12 (1): 3.

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. 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.

PubMed ID: 28202041
PMC ID: PMC5312526
Article link: Neural Dev
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: ckap5 gnl3 slit2 tacc3 tuba4b
Antibodies: Tuba4b Ab14 Tuba4b Ab19 Tuba4b Ab4
Morpholinos: ckap5 MO1 ckap5 MO2 tacc3 MO2


Article Images: [+] show captions
References [+] :
Applegate, plusTipTracker: Quantitative image analysis software for the measurement of microtubule dynamics. 2011, Pubmed