Microtubule-associated protein 1B dysregulates microtubule dynamics and neuronal mitochondrial transport in spinal muscular atrophy
Gamze Bora, Niko Hensel, Sebastian Rademacher, Dila Koyunoğlu, Merve Sunguroğlu, Evrim Aksu‐Menges, Burcu Balcı-Hayta, Peter Claus, Hayat Erdem‐Yurter
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.