Cytoskeleton remodeling Neurofilaments
Neurofilaments
Cytoskeleton of most eukaryotic cells consists of three distinct, yet interconnected,filament systems: actin filaments, microtubules and intermediate filaments(IF). IF network is critically involved in cell shape control and imparts intracellularmechanical strength.
The family of IF proteins has five sub-families: four of them are localized in thecytoplasm and one resides in the nucleus. Cytoplasmic IF proteins such as Vimentin,Desmin, GFAP, Peripherin, Nestin, Desmuslin,alpha-Internexin, Neurofilament triplet proteins ( NEFL, NEFM,NEFH ) form diverse heteropolymers.
Expression patterns of cytoplasmic IFs are cell- and tissue-type specific [1]. Neurofilaments is the principal intermediate filament type expressed byneurons. They are formed by co-assembly of three subunits: NEFL, NEFM,and NEFH.
Peripherin is another IF protein expressed mostly in neurons of the peripheralnervous system. In contrast to neurofilaments, Peripherin can self-assemble toestablish an intermediate filament network. In some cases, Peripherin can assemblewith NEFL. It was suggested that perturbations in the stoichiometry ofneurofilaments can impact Peripherin assembly [2].
Neurofilaments are important protein cargoes for actin -associated motors, suchas myosin, and microtubule -associated motor, such as kinesin in acomplex with Dynactin. These motors are responsible for timely delivery of neuralIF particles and squiggles to all regions of the neuron. Long neural IFs move alongneuritis, albeit more slowly than the precursors.
Munc18, a neuron-specific protein, is independently identified as asyntaxin-binding protein, that regulates kinase activity of cyclin dependent kinase 5 (CDK5 ). Munc18 binds to NEFM and NEFH suggesting its role inthe neuron cytoskeletal dynamics.
IF networks are cross-linked by Plectin 1 and BPAG1 that maintain celland tissue integrity by coordinated interconnection of three distinct cytoskeletalfilament systems [3].
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