Intermediate filaments (IFs) are important intracellular cytoskeletal structures that help to provide eukaryotic cells with shape and structure. Consequently, mutations in IF proteins are associated with several human disorders. The motor neuron disease amyotrophic lateral sclerosis (ALS), for example, is associated with specific isoforms of the IF protein peripherin. Here (p. ), Kay Davies and colleagues suggest that the atypical type-III IF protein syncoilin is also involved in ALS. The authors show first that syncoilin is expressed in the nervous system and that different syncoilin isoforms are dominant in different regions of the nervous system. They then show that syncoilin colocalises with peripherin and present results that suggest that syncoilin modulates the assembly of the peripherin-filament network in vitro by binding to peripherin isoforms. Finally, the authors report that motor performance is reduced in Sync−/− mice compared with wild-type mice, a phenotype that might be caused by an observed shift from large- to small-calibre motor axons in the ventral root of the knockout mice. Together, these data raise the possibility that syncoilin has a role in ALS and in other neuronal diseases that involve IFs.
