The deficiency of survival motor neuron (SMN) protein leads to the dysregulation of several microtubule-associated proteins simultaneously, according to a new study published in Molecular and Cellular Neuroscience. This contributes to the disruption of microtubule dynamics in spinal muscular atrophy (SMA), the authors said.

It was already known that the loss of SMN protein impairs cytoskeletal function and dysregulates microtubules, but the contribution of microtubule-associated proteins to this process was not clear.

In the present study, a team of researchers led by Gamze Bora, PhD, from Hacettepe University, Faculty of Medicine, Department of Medical Biology in Ankara, Turkey used an in vitro model to address the role of neuronal microtubule-associated proteins, which are responsible for the stability and growth of microtubules in SMA. 


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They found that levels of microtubule-associated protein 2 and end-binding 3 (EB3) were decreased in motor neuron-like cells deficient in SMN. Moreover, the level of EB3 protein was relevant to microtubule-associated protein 1B.

Read more about the etiology of SMA

“SMN loss leads to an increase in EB3 comet numbers at proximal neurites, indicating increased microtubule growth,” the researchers wrote, and concluded that their results show that the loss of SMN protein “simultaneously causes dysregulations of several [microtubule-associated proteins].”

The dysregulation of microtubule-associated proteins may in turn affect the stability and dynamics of microtubules and contribute to disease pathology in SMA such as altered axonal transport and F-actin dynamics, they said.

“Understanding the exact players involved in microtubule dysregulations and their functional consequences will help to understand SMA pathomechanisms, which will lead to develop SMN-independent therapeutic strategies in SMA,” they wrote.

SMA is caused by a mutation in the SMN1 gene, which encodes the SMN protein. Motor neurons are particularly vulnerable to SMN protein deficiency and the disease is characterized by muscle weakness and atrophy caused by the loss of lower motor neurons.

Reference

Özer PZ, Koyunoğlu D, Son ÇD, Erdem-Yurtera H, Bora G. SMN loss dysregulates microtubule-associated proteins in spinal muscular atrophy model. Mol Cell Neurosci. Published online April 5, 2022. doi:10.1016/j.mcn.2022.103725.