Neurochondrin interacts with the SMN protein suggesting a novel mechanism for spinal muscular atrophy pathology.

Autor:	Thompson LW; School of Biology, University of St Andrews, BSRC Complex, North Haugh St Andrews, KY16 9ST, UK., Morrison KD; School of Biology, University of St Andrews, BSRC Complex, North Haugh St Andrews, KY16 9ST, UK., Shirran SL; School of Biology, University of St Andrews, BSRC Complex, North Haugh St Andrews, KY16 9ST, UK., Groen EJN; Edinburgh Medical School, Biomedical Sciences and Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK., Gillingwater TH; Edinburgh Medical School, Biomedical Sciences and Euan MacDonald Centre for Motor Neuron Disease Research, University of Edinburgh, Hugh Robson Building, George Square, Edinburgh, EH8 9XD, UK., Botting CH; School of Biology, University of St Andrews, BSRC Complex, North Haugh St Andrews, KY16 9ST, UK., Sleeman JE; School of Biology, University of St Andrews, BSRC Complex, North Haugh St Andrews, KY16 9ST, UK jes14@st-andrews.ac.uk.
Jazyk:	angličtina
Zdroj:	Journal of cell science [J Cell Sci] 2018 Apr 17; Vol. 131 (8). Date of Electronic Publication: 2018 Apr 17.
DOI:	10.1242/jcs.211482
Abstrakt:	Spinal muscular atrophy (SMA) is an inherited neurodegenerative condition caused by a reduction in the amount of functional survival motor neuron (SMN) protein. SMN has been implicated in transport of mRNA in neural cells for local translation. We previously identified microtubule-dependent mobile vesicles rich in SMN and SNRPB, a member of the Sm family of small nuclear ribonucleoprotein (snRNP)-associated proteins, in neural cells. By comparing the interactomes of SNRPB and SNRPN, 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 may have potential as a therapeutic target for SMA together with, or in place of the targeting of SMN expression.This article has an associated First Person interview with the first author of the paper. Competing Interests: Competing interestsThe use of NCDN as a modulator compound for developing SMA therapies is the subject of patent application (L.W.T., J.E.S. and K.D.M.) GB1710433.2 filed 29 June 2017 at the UK Intellectual Property Office. (© 2018. Published by The Company of Biologists Ltd.)
Databáze:	MEDLINE
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