Beat encoding at mistuned octaves within single electrosensory neurons.

Beats are slow periodic amplitude modulations resulting from the superposition of two spectrally close periodic signals. The difference frequency between the signals sets the frequency of the beat. A field study in the electric fish Apteronotus rostratus showed the behavioral relevance of very high difference frequencies. Contrary to expectations from previous studies, our electrophysiological data show strong responses of p-type electroreceptor afferents whenever the difference frequency approaches integer multiples (mistuned octaves) of the fish's own electric field frequency (carrier). Mathematical reasoning and simulations show that common approaches to extract amplitude modulations, such as Hilbert transform or half-wave rectification, are not sufficient to explain the responses at carrier octaves. Instead, half-wave rectification needs to be smoothed out, for example by a cubic function. Because electroreceptive afferents share many properties with auditory nerve fibers, these mechanisms may underly the human perception of beats at mistuned octaves as described by Ohm and Helmholtz.

The Rab5 effector FERRY links early endosomes with mRNA localization.

Localized translation is vital to polarized cells and requires precise and robust distribution of different mRNAs and ribosomes across the cell. However, the underlying molecular mechanisms are poorly understood and important players are lacking. Here, we discovered a Rab5 effector, the five-subunit endosomal Rab5 and RNA/ribosome intermediary (FERRY) complex, that recruits mRNAs and ribosomes to early endosomes through direct mRNA-interaction. FERRY displays preferential binding to certain groups of transcripts, including mRNAs encoding mitochondrial proteins. Deletion of FERRY subunits reduces the endosomal localization of transcripts in cells and has a significant impact on mRNA levels. Clinical studies show that genetic disruption of FERRY causes severe brain damage. We found that, in neurons, FERRY co-localizes with mRNA on early endosomes, and mRNA loaded FERRY-positive endosomes are in close proximity of mitochondria. FERRY thus transforms endosomes into mRNA carriers and plays a key role in regulating mRNA distribution and transport.