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Cold Spring Harb Perspect Biol. 2017 Apr 3;9(4). pii: a018309. doi: 10.1101/cshperspect.a018309.

Neurofilaments and Neurofilament Proteins in Health and Disease.

Yuan A1,2, Rao MV1,2, Veeranna1,2, Nixon RA1,2,3.

Author information

1
Center for Dementia Research, Nathan Kline Institute, Orangeburg, New York 10962.
2
Department of Psychiatry, New York University School of Medicine, New York, New York 10016.
3
Cell Biology, New York University School of Medicine, New York, New York 10016.

Abstract

SUMMARYNeurofilaments (NFs) are unique among tissue-specific classes of intermediate filaments (IFs) in being heteropolymers composed of four subunits (NF-L [neurofilament light]; NF-M [neurofilament middle]; NF-H [neurofilament heavy]; and α-internexin or peripherin), each having different domain structures and functions. Here, we review how NFs provide structural support for the highly asymmetric geometries of neurons and, especially, for the marked radial expansion of myelinated axons crucial for effective nerve conduction velocity. NFs in axons extensively cross-bridge and interconnect with other non-IF components of the cytoskeleton, including microtubules, actin filaments, and other fibrous cytoskeletal elements, to establish a regionally specialized network that undergoes exceptionally slow local turnover and serves as a docking platform to organize other organelles and proteins. We also discuss how a small pool of oligomeric and short filamentous precursors in the slow phase of axonal transport maintains this network. A complex pattern of phosphorylation and dephosphorylation events on each subunit modulates filament assembly, turnover, and organization within the axonal cytoskeleton. Multiple factors, and especially turnover rate, determine the size of the network, which can vary substantially along the axon. NF gene mutations cause several neuroaxonal disorders characterized by disrupted subunit assembly and NF aggregation. Additional NF alterations are associated with varied neuropsychiatric disorders. New evidence that subunits of NFs exist within postsynaptic terminal boutons and influence neurotransmission suggests how NF proteins might contribute to normal synaptic function and neuropsychiatric disease states.

PMID:
28373358
PMCID:
PMC5378049
DOI:
10.1101/cshperspect.a018309
[Indexed for MEDLINE]
Free PMC Article

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