Linked Life Data

16537571

Source:http://linkedlifedata.com/resource/pubmed/id/16537571

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2006-4-3
pubmed:abstractText
The hereditary spastic paraplegias (HSPs) (SPG1-29) comprise a group of inherited neurological disorders characterized principally by spastic lower extremity weakness due to a length-dependent, retrograde axonopathy of corticospinal motor neurons. Mutations in the gene encoding the dynamin superfamily member atlastin-1, an oligomeric GTPase highly localized to the Golgi apparatus in the adult brain, are responsible for SPG3A, a common autosomal dominant HSP. A distinguishing feature of SPG3A is its frequent early onset, raising the possibility that developmental abnormalities may be involved in its pathogenesis. Here, we demonstrate that several missense SPG3A mutant atlastin-1 proteins have impaired GTPase activity and thus may act in a dominant-negative, loss-of-function manner by forming mixed oligomers with wild-type atlastin-1. Using confocal and electron microscopies, we have also found that atlastin-1 is highly enriched in vesicular structures within axonal growth cones and varicosities as well as at axonal branch points in cultured cerebral cortical neurons, prefiguring a functional role for atlastin-1 in axonal development. Indeed, knock-down of atlastin-1 expression in these neurons using small hairpin RNAs reduces the number of neuronal processes and impairs axon formation and elongation during development. Thus, the "long axonopathy" in early-onset SPG3A may result from abnormal development of axons because of loss of atlastin-1 function.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1343-53
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
SPG3A protein atlastin-1 is enriched in growth cones and promotes axon elongation during neuronal development.
pubmed:affiliation
Cellular Neurology Unit, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 35, 35 Convent Drive, Bethesda, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Intramural