Neuronal cell architectural design unveiled
Intermediate filaments (IFs) constitute one of the components of the cytoskeleton and function mechanically to support the cell and its membrane. The expression of specific IF proteins varies between cell types as well as during development and differentiation. These proteins contain large intrinsically disordered regions that do not depend on stable 3D structure to function. This endows them with structural flexibility and plasticity. To further explore these dynamic and flexible biological materials, scientists on the EU-funded IF INTERACTIONS (Self-assembly, structures and interactions of cell specific cytoskeleton) project have used experimental and physical methods to study the intrinsically disordered domains of IFs from the nervous system, known as neurofilaments. The consortium produced five different subunit proteins and, following their structures and interactions when self-assembled into filaments and networks of filaments. Project members used various high resolution imaging techniques, and small-angle X-ray scattering to elucidate the role that different cell-specific IFs play in sustaining mechanical support to neural cells. They found that the properties of filament networks are the result of synergistic interaction between long and short proteins where the latter play a key role in neuronal inter-filament spacing. The research results provide an explanation for the differential expression of neuron IFs during embryonic development. For example, results showed that the inter-filament spacing is reduced from 80 nm in an expanded network when protein subunit α-Inx is expressed during early development to 40 nm postnatally. The network generated from NF-L and NF-M composite filament is condensed and expression of these two proteins increases after birth. The researchers developed a model to explain the expanded network. Their ionic-bridge model views the carboxyl-terminal tails as highly interacting flexible brushes of different properties. This physical model explains how short brushes can give rise to networks with wider inter-filament spacing. Research results of the IF INTERACTIONS study underscore the importance of IFs in maintaining neuronal cellular structure. Given that they may strongly affect cell and tissue functions, their involvement in various diseases needs to be explored. In particular, future research into α-Inx and its exact role should be very important in revealing the complicated architecture of neuronal cells during development.
