Transfer of polyglutamine aggregates in neuronal cells occurs in tunneling nanotubes

• DOI: 10.1242/jcs.126086
• Publication Date: 2013-06-19T02:30:31Z
• Authors: Maddalena Costanzo; Saïda Abounit; Ludovica Marzo; Anne Danckaert; Zeina Chamoun; Pascal Roux; Chiara Zurzolo
• Keywords: Polyglutamine tract; Huntingtin Protein

Huntington's disease (HD) is a dominantly inherited neurodegenerative caused by CAG expansion in the huntingtin gene, which adds homopolymeric tract of polyglutamine (polyQ) to encoded protein leading formation toxic aggregates. Despite rapidly accumulating evidences supporting role for intercellular transmission aggregates, little known about whether and how (Htt) misfolding progresses through brain. It has been recently reported that synthetic polyQ peptides recombinant fragments mutant Htt are readily internalized cell cultures able seed polymerization reporter wild-type Htt. However there no direct evidence aggregate transfer between cells mechanism not explored. By expressing neuronal primary neurons, here we show aggregated formed within one spontaneously neighbors culture. We demonstrate aggregates spreading requires cell-cell contact does occur upon secretion. Interestingly, report expression mutant, but fragments, increases number tunneling nanotubes (TNTs), turn provide an efficient transfer.