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Microtubules and Neurodegeneration: The Tubulin Code Sets the Rules of the Road

J Chloë Bulinski1

  • 1Department of Biological Sciences and Pathology & Cell Biology, Columbia University, 1212 Amsterdam Avenue, New York, NY 10027-2450, USA; Station Biologique de Roscoff, CNRS/Sorbonne Université, Place Georges Teissier, 29688 Roscoff, France.

Current Biology : CB
|January 9, 2019
PubMed

Insights

The tubulin code, a pattern of microtubule modifications, is disrupted when the CCP1 enzyme is removed. This disruption causes neurodegenerative disease and impairs mitochondrial transport, suggesting potential therapeutic targets.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Biochemistry

Background:

  • The 'tubulin code' refers to the specific pattern of post-translational modifications on tubulin proteins within microtubules.
  • Microtubules are essential cytoskeletal components involved in various cellular processes, including intracellular transport and cell division.
  • Dysregulation of the tubulin code has been implicated in various pathologies, including neurodegenerative diseases.

Purpose of the Study:

  • To investigate the role of the enzyme CCP1 in regulating the tubulin code.
  • To determine the consequences of CCP1 disruption on microtubule function and cellular processes.
  • To explore the potential link between CCP1 function and human neurodegenerative diseases.

Main Methods:

  • Utilizing genetic manipulation to delete or mutate the CCP1 enzyme in cellular or model systems.
  • Analyzing the pattern of tubulin modifications using biochemical and imaging techniques.
  • Assessing mitochondrial transport dynamics and cellular health following CCP1 ablation.

Main Results:

  • Deletion or mutation of CCP1 leads to a significant disruption of the established tubulin code.
  • Ablation of CCP1 impairs the proper transport of mitochondria within cells.
  • These findings correlate with the development of phenotypes associated with human neurodegenerative diseases.

Conclusions:

  • CCP1 plays a critical role in maintaining the integrity of the tubulin code.
  • Disruption of the tubulin code by CCP1 deficiency negatively impacts mitochondrial function and transport.
  • Targeting CCP1 or related pathways may offer a novel therapeutic strategy for neurodegenerative disorders.

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