Journal
JOURNAL OF CELL SCIENCE
Volume 115, Issue 24, Pages 4937-4946Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.00148
Keywords
Charcot-Marie-Tooth; intermediate filament; neurofilament; assembly
Categories
Funding
- NIA NIH HHS [AG00189] Funding Source: Medline
- NINDS NIH HHS [NS15182] Funding Source: Medline
Ask authors/readers for more resources
Neurofilaments (NFs) are the major intermediate filaments (IFFs) 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available