Molecular mechanisms underlying the assembly of intermediate filaments

Abstract

The cytoskeleton of animal cells exhibits a dynamic architecture that relies on the interplay of three filament systems, that is, microtubules (MTs), microfilaments (MFs), and intermediate filaments (IFs). They are integrated into a complex, regulated network by associated and cytolinker proteins [1–3]. MTs and MFs are assemblies of globular subunits whose dynamics are controlled by nucleotide hydrolysis. In contrast, IFs assemble without the need of any cofactors from fibrous, coiled-coil forming proteins. These coiled coils are only dissociated at high concentrations of urea. Due to their intrinsic polarity, MTs and MFs serve as tracks for motor proteins to move cargoes, including IFs and their precursors [4]. In contrast, IFs are believed to be structurally nonpolar [5,6], and the integrity of the IF network depends strongly on MTs. This has been demonstrated by the massive rearrangement of IFs within the cytoplasm after disruption of MTs by colcemid [7]. Another key feature of IFs is their resistance against extraction with buffers containing nonionic detergents and high concentrations of salt [8]. This property was originally and is still used to isolate them from cells and tissues. The human body harbors more than 65 different IF proteins that are differentially expressed in complex patterns during embryonic development and that are characteristic for