Home
Deutsch
Advanced Search
Browse by ...
Publication overview
Contact persons
Help
DOI
PMC
 |
|
Open Access Green as soon as Postprint is submitted to ZB.
Mutations in BICD2 cause dominant congenital spinal muscular atrophy and hereditary spastic paraplegia.
Am. J. Hum. Genet. 92, 965-973 (2013)
Dominant congenital spinal muscular atrophy (DCSMA) is a disorder of developing anterior horn cells and shows lower-limb predominance and clinical overlap with hereditary spastic paraplegia (HSP), a lower-limb-predominant disorder of corticospinal motor neurons. We have identified four mutations in bicaudal D homolog 2 (Drosophila) (BICD2) in six kindreds affected by DCSMA, DCSMA with upper motor neuron features, or HSP. BICD2 encodes BICD2, a key adaptor protein that interacts with the dynein-dynactin motor complex, which facilitates trafficking of cellular cargos that are critical to motor neuron development and maintenance. We demonstrate that mutations resulting in amino acid substitutions in two binding regions of BICD2 increase its binding affinity for the cytoplasmic dynein-dynactin complex, which might result in the perturbation of BICD2-dynein-dynactin-mediated trafficking, and impair neurite outgrowth. These findings provide insight into the mechanism underlying both the static and the slowly progressive clinical features and the motor neuron pathology that characterize BICD2-associated diseases, and underscore the importance of the dynein-dynactin transport pathway in the development and survival of both lower and upper motor neurons.
Altmetric
Additional Metrics?
Edit extra informations
Login
Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Bicaudal-d ; Transport ; Oogenesis ; Neurons ; Genome ; Form
ISSN (print) / ISBN
0002-9297
e-ISSN
1537-6605
Quellenangaben
Volume: 92,
Issue: 6,
Pages: 965-973
Publisher
Elsevier
Publishing Place
New York, NY
Reviewing status
Peer reviewed
Institute(s)
Institute of Human Genetics (IHG)