dominant spinal muscular atrophy is caused by mutations in bicd2, an important golgin protein

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ID: 160487
2015
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Abstract
Spinal muscular atrophies (SMAs) are characterized by degeneration of spinal motor neurons and muscle weakness. Autosomal recessive SMA is the most common form and is caused by homozygous deletions/mutations of the SMN1 gene. However, families with dominant inherited SMA have been reported, for most of them the causal gene remains unknown. Recently, we and others have identified heterozygous mutations in BICD2 as causative for autosomal dominant SMA, lower extremity-predominant, 2 (SMALED2). BICD2 encodes the Bicaudal D2 protein, which is considered to be a golgin, due to its coiled-coil structure and interaction with the small GTPase RAB6A located at the Golgi apparatus. Golgins are resident proteins in the Golgi apparatus and form a matrix that helps to maintain the structure of this organelle. Golgins are also involved in the regulation of vesicle transport. In vitro overexpression experiments and studies of fibroblast cell lines derived from patients, showed fragmentation of the Golgi apparatus. In the current review, we will discuss possible causes for this disruption and the consequences at cellular level, with a view to better understand the pathomechanism of this disease.
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ewirth2015frontiersdominant Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors ;Brunhilde eWirth;Brunhilde eWirth;Brunhilde eWirth;Lilian A. Martinez-Carrera;Lilian A. Martinez-Carrera;Lilian A. Martinez-Carrera
Journal Journal of enzyme inhibition and medicinal chemistry
Year 2015
DOI
10.3389/fnins.2015.00401
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