4.8 Article

Microtubule retrograde flow retains neuronal polarization in a fluctuating state

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SCIENCE ADVANCES
卷 8, 期 44, 页码 -

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AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.abo2336

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资金

  1. Deutsche Forschungsgesellschaft (DFG)
  2. International Foundation for Research in Paraplegia (IRP)
  3. Wings for Life
  4. Add-On Fellowship for Interdisciplinary Sciences from the Joachim Herz Foundation
  5. International Max Planck Research School for Brain and Behavior (IMPRS-BB)
  6. Roger De Spoelberch Prize

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In developing vertebrate neurons, microtubules flow retrogradely within the neurites to the soma, inhibiting neurite growth. However, shortly after axon formation, microtubule retrograde flow slows down, enabling axon extension.
In developing vertebrate neurons, a neurite is formed by more than a hundred microtubules. While individual microtubules are dynamic, the microtubule array has been regarded as stationary. Using live-cell imaging of neurons in culture or in brain slices, combined with photoconversion techniques and pharmacological manipulations, we uncovered that the microtubule array flows retrogradely within neurites to the soma. This flow drives cycles of microtubule density, a hallmark of the fluctuating state before axon formation, thereby inhibiting neurite growth. The motor protein dynein fuels this process. Shortly after axon formation, microtubule retrograde flow slows down in the axon, reducing microtubule density cycles and enabling axon extension. Thus, keeping neurites short is an active process. Microtubule retrograde flow is a previously unknown type of cytoskeletal dynamics, which changes the hitherto axon-centric view of neuronal polarization.

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