A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons - PubMed (original) (raw)
doi: 10.1038/ncb1139. Epub 2004 Jun 20.
Affiliations
- PMID: 15208636
- DOI: 10.1038/ncb1139
A NUDEL-dependent mechanism of neurofilament assembly regulates the integrity of CNS neurons
Minh Dang Nguyen et al. Nat Cell Biol. 2004 Jul.
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.
Comment in
- Tangled NUDELs?
Holzbaur EL. Holzbaur EL. Nat Cell Biol. 2004 Jul;6(7):569-70. doi: 10.1038/ncb0704-569. Nat Cell Biol. 2004. PMID: 15232582 No abstract available.
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