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 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.

SUBMITTER: Thompson LW 

PROVIDER: S-EPMC5963842 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature