Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology

Luke W. Thompson; Kim D.  Morrison; Sally L. Shirran; Ewout J. N. Groen; Tom H. Gillingwater; Catherine H. Botting; Judith E. Sleeman

doi:10.1242/jcs.211482

Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology

Luke W. Thompson, Kim D. Morrison, Sally L. Shirran, Ewout J. N. Groen, Tom H. Gillingwater, Catherine H. Botting, Judith E. Sleeman

Research output: Contribution to journal › Article › peer-review

Abstract

Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN). SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependant mobile vesicles rich in SMN and the splicing factor SmB, a member of the Sm protein family, in neural cells. By comparing the proteome of SmB to that of SmN, a neural-specific Sm protein, we now show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites. NCDN has roles in protein localisation in neural cells, and in maintenance of cell polarity. NCDN is required for the correct localisation of SMN, suggesting they may both be required for formation and transport of trafficking vesicles. NCDN provides a potential therapeutic target for SMA together with, or in place of, those targeting SMN expression.

Original language	English
Article number	jcs211482
Number of pages	18
Journal	Journal of Cell Science
Volume	131
Issue number	8
DOIs	https://doi.org/10.1242/jcs.211482
Publication status	Published - 17 Apr 2018

Keywords

Spinal Muscular Atrophy
Neurochondrin
SMN
Sm proteins
snRNPs

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Thompson-2018-Neurochondrin-jcs211482-CC
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Cite this

@article{84153cbb83db4ed2a1a6e389e0a1e33f,

title = "Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology",

abstract = "Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN). SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependant mobile vesicles rich in SMN and the splicing factor SmB, a member of the Sm protein family, in neural cells. By comparing the proteome of SmB to that of SmN, a neural-specific Sm protein, we now show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites. NCDN has roles in protein localisation in neural cells, and in maintenance of cell polarity. NCDN is required for the correct localisation of SMN, suggesting they may both be required for formation and transport of trafficking vesicles. NCDN provides a potential therapeutic target for SMA together with, or in place of, those targeting SMN expression.",

keywords = "Spinal Muscular Atrophy, Neurochondrin, SMN, Sm proteins, snRNPs",

author = "Thompson, {Luke W.} and Morrison, {Kim D.} and Shirran, {Sally L.} and Groen, {Ewout J. N.} and Gillingwater, {Tom H.} and Botting, {Catherine H.} and Sleeman, {Judith E.}",

note = "Work in the Sleeman laboratory by Luke Thompson was funded by MRC-CASE studentship MR/K016997/1. This work was also supported by the Wellcome Trust [grant number 094476/Z/10/Z], which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews.",

year = "2018",

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doi = "10.1242/jcs.211482",

language = "English",

volume = "131",

journal = "Journal of Cell Science",

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T1 - Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology

AU - Thompson, Luke W.

AU - Morrison, Kim D.

AU - Shirran, Sally L.

AU - Groen, Ewout J. N.

AU - Gillingwater, Tom H.

AU - Botting, Catherine H.

AU - Sleeman, Judith E.

N1 - Work in the Sleeman laboratory by Luke Thompson was funded by MRC-CASE studentship MR/K016997/1. This work was also supported by the Wellcome Trust [grant number 094476/Z/10/Z], which funded the purchase of the TripleTOF 5600 mass spectrometer at the BSRC Mass Spectrometry and Proteomics Facility, University of St Andrews.

PY - 2018/4/17

Y1 - 2018/4/17

N2 - Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN). SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependant mobile vesicles rich in SMN and the splicing factor SmB, a member of the Sm protein family, in neural cells. By comparing the proteome of SmB to that of SmN, a neural-specific Sm protein, we now show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites. NCDN has roles in protein localisation in neural cells, and in maintenance of cell polarity. NCDN is required for the correct localisation of SMN, suggesting they may both be required for formation and transport of trafficking vesicles. NCDN provides a potential therapeutic target for SMA together with, or in place of, those targeting SMN expression.

AB - Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN). SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependant mobile vesicles rich in SMN and the splicing factor SmB, a member of the Sm protein family, in neural cells. By comparing the proteome of SmB to that of SmN, a neural-specific Sm protein, we now show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites. NCDN has roles in protein localisation in neural cells, and in maintenance of cell polarity. NCDN is required for the correct localisation of SMN, suggesting they may both be required for formation and transport of trafficking vesicles. NCDN provides a potential therapeutic target for SMA together with, or in place of, those targeting SMN expression.

KW - Spinal Muscular Atrophy

KW - Neurochondrin

KW - SMN

KW - Sm proteins

KW - snRNPs

UR - https://doi.org/10.1101/183640

U2 - 10.1242/jcs.211482

DO - 10.1242/jcs.211482

M3 - Article

C2 - 29507115

SN - 0021-9533

VL - 131

JO - Journal of Cell Science

JF - Journal of Cell Science

IS - 8

M1 - jcs211482

ER -

Neurochondrin interacts with the SMN protein suggesting a novel mechanism for Spinal Muscular Atrophy pathology

Abstract

Keywords

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Luke Thompson Studentship: Characterization of cytoplasmic trafficking vesicles implicated in the pathology of spinal muscular atrophy.

MaXis ESI QTOF mass spectrometer: Equipment only grant-Mass spectrometers for Proteomics, Lipidomics and focused Metabolomics research

Judith Elizabeth Sleeman