Abstract
ABSTRACTSpinal 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.
Highlights
The inherited neurodegenerative disease, Spinal Muscular Atrophy (SMA) is caused by a reduction in the amount of functional Survival Motor Neuron (SMN) protein (Lefebvre et al, 1995)
Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative condition caused by reduction in functional Survival Motor Neurones Protein (SMN)
By comparing the interactomes of SmB and SmN, a neural-specific Sm protein, we show that the essential neural protein neurochondrin (NCDN) interacts with Sm proteins and SMN in the context of mobile vesicles in neurites
Summary
The inherited neurodegenerative disease, Spinal Muscular Atrophy (SMA) is caused by a reduction in the amount of functional Survival Motor Neuron (SMN) protein (Lefebvre et al, 1995). Due to the small amounts of full length SMN expressed from the SMN2 gene, the number of gene copies can influence the severity of SMA, with evidence that five copies of SMN2 may be enough to compensate for loss of SMN1 (Campbell et al, 1997; Prior et al, 2004). It is not currently clear how a deficiency of functional SMN leads to the specific symptoms of SMA. The differing sensitivity of cell types to lowered SMN levels, with motor neurons (MNs) most severely affected, is difficult to explain as SMN is an essential protein and complete deletion is lethal at the cellular level (Hsieh-Li et al, 2000; Schrank et al, 1997)
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