title: Composite bottlebrush mechanics: α-internexin fine-tunes neurofilament network properties.
abstract: Neuronal cytoplasmic intermediate filaments are principal structural and mechanical elements of the axon. Their expression during embryonic development follows a differential pattern, while their unregulated expression is correlated to neurodegenerative diseases. The largest neurofilament proteins of medium (NF-M) and high molecular weight (NF-H) were shown to modulate the axonal architecture and inter-filament spacing. However, the individual roles of the remaining α-internexin (α-Inx) and neurofilament of low molecular weight (NF-L) proteins in composite filaments remained elusive. In contrast to previous predictions, we show that when co-assembled with NF-M, the shortest and the least charged α-Inx protein increases inter-filament spacing. These findings suggest a novel structural explanation for the expression pattern of neurofilament proteins during embryonic development. We explain our results by an analysis of ionic cross-links between the disordered polyampholytic C-terminal tails and suggest that a collapsed conformation of the α-Inx tail domain interferes with tail cross-linking near the filament backbone.
authors.affiliation: The Raymond and Beverly Sackler School of Physics and Astronomy, Tel-Aviv University, 69978 Tel Aviv, Israel. roy@post.tau.ac.il.
authors.forename: M
authors.initials: M
authors.lastname: Kornreich
authors.forename: E
authors.initials: E
authors.lastname: Malka-Gibor
authors.forename: A
authors.initials: A
authors.lastname: Laser-Azogui
authors.forename: O
authors.initials: O
authors.lastname: Doron
authors.forename: H
authors.initials: H
authors.lastname: Herrmann
authors.forename: R
authors.initials: R
authors.lastname: Beck
mesh_terms: D001369:Axons / Q000737:chemistry / Q000378:metabolism; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry; D057927:Hydrophobic and Hydrophilic Interactions; D007381:Intermediate Filament Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D007382:Intermediate Filaments / Q000737:chemistry*; D016900:Neurofilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D009997:Osmotic Pressure; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000302:isolation & purification; D053838:Scattering, Small Angle; D055672:Static Electricity; D014961:X-Ray Diffraction
chemical_list: D007381:Intermediate Filament Proteins; D016900:Neurofilament Proteins; D011994:Recombinant Proteins; C046643:alpha-internexin; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate