Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                      What's this?

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 also had similar effects: nicotine, which stimulates neurons, promoted aggregation, as did an insecticide called lindane, which inhibits GABA.

"It is a stunning surprise that a transcription factor expressed only in the presynaptic cell can have such a profound effect on aggregation in the postsynaptic cell," Morimoto says. The researchers are planning to seek evidence for similar effects in other communicating cells.

The polyglutamine protein used in these experiments contains just enough glutamines to be at the threshold of aggregation and is therefore exquisitely sensitive to outside influences. "Environment can play a big role in tipping the balance in such systems," says Morimoto. The effects may help explain why polyglutamine diseases such as Huntington's arise at different times in siblings with identical repeat lengths.

Reference:

Garcia, S.M., et al. 2007. Genes Dev. 21:3006–3016.[Abstract/Free Full Text]

Richard Robinson

rrobinson{at}nasw.org

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This Article PDF (Full Text) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Robinson, R. Search for Related Content PubMed Articles by Robinson, R. Social Bookmarking                      What's this?