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  • Non-enzymatic Activity of the α-Tubulin Acetyltransferase αTAT Limits Synaptic Bouton Growth in Neurons.

Non-enzymatic Activity of the α-Tubulin Acetyltransferase αTAT Limits Synaptic Bouton Growth in Neurons.

Current biology : CB (2020-01-14)
Courtney E Coombes, Harriet A J Saunders, Anirudh G Mannava, Dena M Johnson-Schlitz, Taylor A Reid, Sneha Parmar, Mark McClellan, Connie Yan, Stephen L Rogers, Jay Z Parrish, Michael Wagenbach, Linda Wordeman, Jill Wildonger, Melissa K Gardner
摘要

Neuronal axons terminate as synaptic boutons that form stable yet plastic connections with their targets. Synaptic bouton development relies on an underlying network of both long-lived and dynamic microtubules that provide structural stability for the boutons while also allowing for their growth and remodeling. However, a molecular-scale mechanism that explains how neurons appropriately balance these two microtubule populations remains a mystery. We hypothesized that α-tubulin acetyltransferase (αTAT), which both stabilizes long-lived microtubules against mechanical stress via acetylation and has been implicated in promoting microtubule dynamics, could play a role in this process. Using the Drosophila neuromuscular junction as a model, we found that non-enzymatic dαTAT activity limits the growth of synaptic boutons by affecting dynamic, but not stable, microtubules. Loss of dαTAT results in the formation of ectopic boutons. These ectopic boutons can be similarly suppressed by resupplying enzyme-inactive dαTAT or by treatment with a low concentration of the microtubule-targeting agent vinblastine, which acts to suppress microtubule dynamics. Biophysical reconstitution experiments revealed that non-enzymatic αTAT1 activity destabilizes dynamic microtubules but does not substantially impact the stability of long-lived microtubules. Further, during microtubule growth, non-enzymatic αTAT1 activity results in increasingly extended tip structures, consistent with an increased rate of acceleration of catastrophe frequency with microtubule age, perhaps via tip structure remodeling. Through these mechanisms, αTAT enriches for stable microtubules at the expense of dynamic ones. We propose that the specific suppression of dynamic microtubules by non-enzymatic αTAT activity regulates the remodeling of microtubule networks during synaptic bouton development.

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牛血清白蛋白 来源于牛血清, heat shock fraction, pH 7, ≥98%
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明胶 来源于冷水鱼类的皮肤, 40-50% in H2O
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抗-α-微管蛋白抗体,小鼠单克隆, clone DM1A, purified from hybridoma cell culture
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紫杉醇, from semisynthetic, ≥98%
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乙酰化微管蛋白单克隆抗体 小鼠抗, clone 6-11B-1, ascites fluid
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Triton X-100, laboratory grade
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Vinblastine sulfate salt, ≥97% (HPLC)