Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of schwann cell defects in spinal muscular atrophy

Arwin Aghamaleky Sarvestany, Gillian Hunter, Amy Tavendale, Douglas Lamont, Maica Llavero Hurtado, Laura Graham, Thomas Wishart, Thomas Gillingwater

Research output: Contribution to journalArticle

Abstract

Low levels of survival of motor neuron (SMN) protein cause the neuromuscular disease spinal muscular atrophy (SMA), characterized by degeneration of lower motor neurons and atrophy of skeletal muscle. Recent work demonstrated that low levels of SMN also trigger pathological changes in Schwann cells, leading to abnormal axon myelination and disrupted deposition of extracellular matrix proteins in peripheral nerve. However, the molecular pathways linking SMN depletion to intrinsic defects in Schwann cells remained unclear. Label-free proteomics analysis of Schwann cells isolated from SMA mouse peripheral nerve revealed widespread changes to the Schwann cell proteome, including disruption to growth/proliferation, cell death/survival, and molecular transport pathways. Functional clustering analyses revealed significant disruption to a number of proteins contributing to ubiquitination pathways, including reduced levels of ubiquitin-like modifier activating enzyme 1 (Uba1).
Original languageEnglish
Pages (from-to)4546-4557
Number of pages12
JournalJournal of Proteome Research
Volume13
Issue number11
Early online date29 Aug 2014
DOIs
Publication statusPublished - 2014

Fingerprint

Spinal Muscular Atrophy
Schwann Cells
Motor Neurons
Ubiquitin
Proteomics
Neurons
Labels
Homeostasis
Cells
Defects
Peripheral Nerves
Neuromuscular Diseases
Extracellular Matrix Proteins
Ubiquitination
Cell death
Proteome
Atrophy
Cluster Analysis
Axons
Muscle

Keywords

  • proteomic profiling
  • spinal muscular atrophy
  • motor neurons

Cite this

Aghamaleky Sarvestany, Arwin ; Hunter, Gillian ; Tavendale, Amy ; Lamont, Douglas ; Llavero Hurtado, Maica ; Graham, Laura ; Wishart, Thomas ; Gillingwater, Thomas. / Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of schwann cell defects in spinal muscular atrophy. In: Journal of Proteome Research. 2014 ; Vol. 13, No. 11. pp. 4546-4557.
@article{e820bb0aeb0245429e37ccd3487dd0ba,
title = "Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of schwann cell defects in spinal muscular atrophy",
abstract = "Low levels of survival of motor neuron (SMN) protein cause the neuromuscular disease spinal muscular atrophy (SMA), characterized by degeneration of lower motor neurons and atrophy of skeletal muscle. Recent work demonstrated that low levels of SMN also trigger pathological changes in Schwann cells, leading to abnormal axon myelination and disrupted deposition of extracellular matrix proteins in peripheral nerve. However, the molecular pathways linking SMN depletion to intrinsic defects in Schwann cells remained unclear. Label-free proteomics analysis of Schwann cells isolated from SMA mouse peripheral nerve revealed widespread changes to the Schwann cell proteome, including disruption to growth/proliferation, cell death/survival, and molecular transport pathways. Functional clustering analyses revealed significant disruption to a number of proteins contributing to ubiquitination pathways, including reduced levels of ubiquitin-like modifier activating enzyme 1 (Uba1).",
keywords = "proteomic profiling, spinal muscular atrophy, motor neurons",
author = "{Aghamaleky Sarvestany}, Arwin and Gillian Hunter and Amy Tavendale and Douglas Lamont and {Llavero Hurtado}, Maica and Laura Graham and Thomas Wishart and Thomas Gillingwater",
note = "Publisher version not permitted in repositories, set to back end vis. ET 30-11-15",
year = "2014",
doi = "10.1021/pr500492j",
language = "English",
volume = "13",
pages = "4546--4557",
journal = "Journal of Proteome Research",
issn = "1535-3893",
publisher = "American Chemical Society",
number = "11",

}

Aghamaleky Sarvestany, A, Hunter, G, Tavendale, A, Lamont, D, Llavero Hurtado, M, Graham, L, Wishart, T & Gillingwater, T 2014, 'Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of schwann cell defects in spinal muscular atrophy', Journal of Proteome Research, vol. 13, no. 11, pp. 4546-4557. https://doi.org/10.1021/pr500492j

Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of schwann cell defects in spinal muscular atrophy. / Aghamaleky Sarvestany, Arwin; Hunter, Gillian; Tavendale, Amy; Lamont, Douglas; Llavero Hurtado, Maica; Graham, Laura; Wishart, Thomas; Gillingwater, Thomas.

In: Journal of Proteome Research, Vol. 13, No. 11, 2014, p. 4546-4557.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Label-free quantitative proteomic profiling identifies disruption of ubiquitin homeostasis as a key driver of schwann cell defects in spinal muscular atrophy

AU - Aghamaleky Sarvestany, Arwin

AU - Hunter, Gillian

AU - Tavendale, Amy

AU - Lamont, Douglas

AU - Llavero Hurtado, Maica

AU - Graham, Laura

AU - Wishart, Thomas

AU - Gillingwater, Thomas

N1 - Publisher version not permitted in repositories, set to back end vis. ET 30-11-15

PY - 2014

Y1 - 2014

N2 - Low levels of survival of motor neuron (SMN) protein cause the neuromuscular disease spinal muscular atrophy (SMA), characterized by degeneration of lower motor neurons and atrophy of skeletal muscle. Recent work demonstrated that low levels of SMN also trigger pathological changes in Schwann cells, leading to abnormal axon myelination and disrupted deposition of extracellular matrix proteins in peripheral nerve. However, the molecular pathways linking SMN depletion to intrinsic defects in Schwann cells remained unclear. Label-free proteomics analysis of Schwann cells isolated from SMA mouse peripheral nerve revealed widespread changes to the Schwann cell proteome, including disruption to growth/proliferation, cell death/survival, and molecular transport pathways. Functional clustering analyses revealed significant disruption to a number of proteins contributing to ubiquitination pathways, including reduced levels of ubiquitin-like modifier activating enzyme 1 (Uba1).

AB - Low levels of survival of motor neuron (SMN) protein cause the neuromuscular disease spinal muscular atrophy (SMA), characterized by degeneration of lower motor neurons and atrophy of skeletal muscle. Recent work demonstrated that low levels of SMN also trigger pathological changes in Schwann cells, leading to abnormal axon myelination and disrupted deposition of extracellular matrix proteins in peripheral nerve. However, the molecular pathways linking SMN depletion to intrinsic defects in Schwann cells remained unclear. Label-free proteomics analysis of Schwann cells isolated from SMA mouse peripheral nerve revealed widespread changes to the Schwann cell proteome, including disruption to growth/proliferation, cell death/survival, and molecular transport pathways. Functional clustering analyses revealed significant disruption to a number of proteins contributing to ubiquitination pathways, including reduced levels of ubiquitin-like modifier activating enzyme 1 (Uba1).

KW - proteomic profiling

KW - spinal muscular atrophy

KW - motor neurons

U2 - 10.1021/pr500492j

DO - 10.1021/pr500492j

M3 - Article

VL - 13

SP - 4546

EP - 4557

JO - Journal of Proteome Research

JF - Journal of Proteome Research

SN - 1535-3893

IS - 11

ER -