title: Structures and interactions in 'bottlebrush' neurofilaments: the role of charged disordered proteins in forming hydrogel networks.
abstract: NFs (neurofilaments), the major cytoskeletal constituent of myelinated axons in vertebrates, consist of three different molecular-mass subunit proteins, NF-L (low), NF-M (medium) and NF-H (high), assembled to form mature filaments with protruding intrinsically disordered C-terminal side-arms. Liquid crystal gel networks of side-arm-mediated NF assemblies play a key role in the mechanical stability of neuronal processes. Disruptions of the NF network, due to NF overaccumulation or incorrect side-arm interactions, are a hallmark of motor neuron diseases including amyotrophic lateral sclerosis. Using synchrotron small-angle X-ray scattering and various microscopy techniques, we have investigated the role of the peptide charges in the subunit side-arms on the structure and interaction of NFs. Our findings, which delineate the distinct roles of NF-M and NF-H in regulating NF interactions, shed light on possible mechanisms of disruption of optimal mechanical network properties.
authors.affiliation: School of Physics and Astronomy, Tel Aviv University, 69978 Tel Aviv, Israel. roy@post.tau.ac.il
authors.forename: Roy
authors.initials: R
authors.lastname: Beck
authors.forename: Joanna
authors.initials: J
authors.lastname: Deek
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Safinya
mesh_terms: D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry* / Q000378:metabolism; D056004:Molecular Dynamics Simulation; D009010:Monte Carlo Method; D016900:Neurofilament Proteins / Q000737:chemistry* / Q000378:metabolism; D009474:Neurons / Q000737:chemistry / Q000378:metabolism; D011487:Protein Conformation
chemical_list: D016900:Neurofilament Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate