Plexin-Semaphorin Signaling Modifies Neuromuscular Defects in a Drosophila Model of Peripheral Neuropathy.

ABSTRACT: Dominant mutations in GARS, encoding the ubiquitous enzyme glycyl-tRNA synthetase (GlyRS), cause peripheral nerve degeneration and Charcot-Marie-Tooth disease type 2D (CMT2D). This genetic disorder exemplifies a recurring paradigm in neurodegeneration, in which mutations in essential genes cause selective degeneration of the nervous system. Recent evidence suggests that the mechanism underlying CMT2D involves extracellular neomorphic binding of mutant GlyRS to neuronally-expressed proteins. Consistent with this, our previous studies indicate a non-cell autonomous mechanism, whereby mutant GlyRS is secreted and interacts with the neuromuscular junction (NMJ). In this Drosophila model for CMT2D, we have previously shown that mutant gars expression decreases viability and

SUBMITTER: Grice SJ 

PROVIDER: S-EPMC5827687 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature