Mutation of a neuronal transcription factor that activates neurons causes protein misfolding and aggregation (green) in worm muscle cells.

MORIMOTO/CSHL

An overactive neuron can cause protein aggregation in its target cell, according to new work by Susana Garcia, Richard Morimoto (Northwestern University, Evanston, IL), and colleagues, indicating that actions of one cell may disrupt protein homeostasis in another.

The authors discovered that mutations in a transcription factor found only in neurons increased aggregation of polyglutamine-containing proteins in muscle cells in C. elegans. This factor, UNC-30, boosts synthesis of GABA, which inhibits neuronal firing. Increased protein aggregation also resulted from other GABA-reducing (and thus neuronal stimulating) mutations, including one in the muscle cell's GABA receptor.

GABA's normal actions are counteracted by the stimulatory neurotransmitter acetylcholine. Mutation-induced overactivity of the acetylcholine system had the same effect on polyglutamine aggregation as too little GABA activity. Small molecules...

The Rockefeller University Press
2007
The Rockefeller University Press
2007
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