A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons
SCIE
SCOPUS
- Title
- A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons
- Authors
- Nguyen, MD; Shu, TZ; Sanada, K; Lariviere, RC; Tseng, HC; Park, SK; Julien, JP; Tsai, LH
- Date Issued
- 2004-07
- Publisher
- NATURE PUBLISHING GROUP
- Abstract
- The cytoskeleton controls the architecture and survival of central nervous system (CNS) neurons by maintaining the stability of axons and dendrites. Although neurofilaments (NFs) constitute the main cytoskeletal network in these structures, the mechanism that underlies subunit incorporation into filaments remains a mystery. Here we report that NUDEL, a mammalian homologue of the Aspergillus nidulans nuclear distribution molecule NudE, is important for NF assembly, transport and neuronal integrity. NUDEL facilitates the polymerization of NFs through a direct interaction with the NF light subunit (NF-L). Knockdown of NUDEL by RNA interference (RNAi) in a neuroblastoma cell line, primary cortical neurons or post-natal mouse brain destabilizes NF-L and alters the homeostasis of NFs. This results in NF abnormalities and morphological changes reminiscent of neurodegeneration. Furthermore, variations in levels of NUDEL correlate with disease progression and NF defects in a mouse model of neurodegeneration. Thus, NUDEL contributes to the integrity of CNS neurons by regulating NF assembly.
- Keywords
- AMYOTROPHIC-LATERAL-SCLEROSIS; MUTANT SUPEROXIDE-DISMUTASE; INTERMEDIATE-FILAMENTS; NERVOUS-SYSTEM; MOUSE MODEL; MICROTUBULE ORGANIZATION; CYTOPLASMIC DYNEIN; AXONAL-TRANSPORT; GENE-EXPRESSION; SOD1 MUTATION
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/28379
- DOI
- 10.1038/NCB1139
- ISSN
- 1465-7392
- Article Type
- Article
- Citation
- NATURE CELL BIOLOGY, vol. 6, no. 7, page. 595 - 608, 2004-07
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.