Type 2 Neurofilament Research from Columbia University USA

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1: J Cell Sci 2002 Dec 15;115(Pt 24):4937-46

Effects of Charcot-Marie-Tooth-linked mutations of the neurofilament

light subunit on intermediate filament formation.

-Olle R, Leung CL, Liem RK.

Department of Pathology, Columbia University College of Physicians &

Surgeons, 630 West 168th Street, New York, NY 10032, USA.

Neurofilaments (NFs) are the major intermediate filaments (IFs) of

mature neurons. They play important roles in the structure and function

of axons. Recently, two mutations in the neurofilament light (NFL)

subunit have been identified in families affected by Charcot-Marie-Tooth

(CMT) neuropathy type 2. We have characterized the effects of these NFL

mutations on the formation of IF networks using a transient transfection

system. Both mutations disrupted the self-assembly of human NFL. The

Q333P mutant in the rod domain of NFL also disrupted the formation of

rat and human NFL/NFM heteropolymers. The phenotypes produced by the P8R

mutation in the head

domain of NFL were less severe. The P8R mutant NFL co-polymerized with

NFM to form bundled filaments and, less often, aggregates. Our results

suggest that alterations in the formation of a normal IF network in

neurons elicited by these NFL mutations may contribute to the

development of Charcot-Marie-Tooth neuropathy.