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Updated: Apr 10, 2026

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Microtubules in the axon are GDP bound but adopt a stable GTP-like expanded state

Elena A Zehr1, Shufeng Sun1, Stephanie L Sarbanes1

  • 1Cell Biology and Biophysics Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

Nature Structural & Molecular Biology
|April 8, 2026
PubMed

Insights

Human neurons have expanded microtubule lattices, even when GDP-bound, unlike undifferentiated cells. This lattice expansion is key to neuronal differentiation and neurogenesis.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Structural Biology

Background:

  • Microtubules are essential cellular structures involved in signaling and transport.
  • Tubulin polymerization and GTP hydrolysis influence microtubule stability.
  • The in vivo conformation of tubulin within cellular microtubules remains largely unknown.

Purpose of the Study:

  • To determine the atomic structure of human microtubules in situ within neuronal axons.
  • To investigate the conformational state of tubulin in differentiated neurons compared to undifferentiated cells.
  • To elucidate the role of microtubule lattice structure in neuronal differentiation.

Main Methods:

  • Atomic-resolution cryo-electron microscopy (cryo-EM) of human microtubules in axons.
  • Cryo-electron tomography (cryo-ET) and power spectrum analysis of microtubules in iPS cells and neurons.
  • Analysis of tubulin conformation and lattice spacing in different cellular contexts.

Main Results:

  • Revealed the 2.7-Å resolution cryo-EM structure of human microtubules in neuronal axons.
  • Demonstrated that axonal microtubules adopt an expanded, GTP-like lattice despite GDP-tubulin binding.
  • Observed compacted microtubule lattices in undifferentiated iPS cells, contrasting with the expanded state in neurons.

Conclusions:

  • Microtubule lattice expansion is a feature of neuronal differentiation.
  • The expanded lattice structure in neurons, even when GDP-bound, provides molecular insights into neurogenesis.
  • Findings have implications for understanding microtubule stability and effector protein interactions in the nervous system.

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