Microtubule-associated protein 1B dysregulates microtubule dynamics and neuronal mitochondrial transport in spinal muscular atrophy.


Bora G. , Hensel N., Rademacher S., Koyunoğlu D., Sunguroğlu M., Aksu-Mengeş E., ...More

Human molecular genetics, vol.29, pp.3935-3944, 2021 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 29
  • Publication Date: 2021
  • Doi Number: 10.1093/hmg/ddaa275
  • Title of Journal : Human molecular genetics
  • Page Numbers: pp.3935-3944

Abstract

Spinal muscular atrophy (SMA) is a devastating childhood disease primarily affecting lower motoneurons in the spinal cord. SMA is caused by the loss of functional survival of motoneuron (SMN) protein, leading to structural and functional alterations of the cytoskeleton in motoneurons and other cells. Loss of SMN results in impairments of microtubule architecture, but the underlying mechanisms are not completely understood. In this study, we mechanistically analyzed the effects of SMN deficiency on microtubules, demonstrating a reduced stability together with a reduction in alpha tubulin detyrosination. This was caused by increased levels of microtubule-associated protein 1B and tubulin tyrosine ligase, resulting in mitochondrial mislocalization in SMA. Our findings suggest that altered tubulin post-translational modifications and microtubule-associated proteins are involved in the pathomechanisms of SMA, such as an impaired axonal transport of mitochondria.