Stability dynamics of neurofilament and GFAP networks and protein fragments

Cassandra L Phillips; Maryam Faridounnia; Diane Armao; Natasha T Snider

doi:10.1016/j.ceb.2023.102266

Stability dynamics of neurofilament and GFAP networks and protein fragments

Curr Opin Cell Biol. 2023 Dec:85:102266. doi: 10.1016/j.ceb.2023.102266. Epub 2023 Oct 20.

Authors

Cassandra L Phillips¹, Maryam Faridounnia¹, Diane Armao², Natasha T Snider³

Affiliations

¹ Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, USA.
² Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, USA; Department of Radiology, University of North Carolina at Chapel Hill, USA.
³ Department of Cell Biology and Physiology, University of North Carolina at Chapel Hill, USA. Electronic address: ntsnider@med.unc.edu.

PMID: 37866019
DOI: 10.1016/j.ceb.2023.102266

Abstract

Neurofilaments (NFs) and GFAP are cytoskeletal intermediate filaments (IFs) that support cellular processes unfolding within the uniquely complex environments of neurons and astrocytes, respectively. This review highlights emerging concepts on the transitions between stable and destabilized IF networks in the nervous system. While self-association between transiently structured low-complexity IF domains promotes filament assembly, the opposing destabilizing actions of phosphorylation-mediated filament severing facilitate faster intracellular transport. Cellular proteases, including caspases and calpains, produce a variety of IF fragments, which may interact with N-degron and C-degron pathways of the protein degradation machinery. The rapid adoption of NF and GFAP-based clinical biomarker tests is contrasted with the lagging understanding of the dynamics between the native IF proteins and their fragments.

Publication types

Review

MeSH terms

Cytoskeleton* / metabolism
Intermediate Filaments* / metabolism
Nervous System
Neurons
Phosphorylation