Spectrin mutations cause spinocerebellar ataxia type 5.
Nat Genet
; 38(2): 184-90, 2006 Feb.
Article
en En
| MEDLINE
| ID: mdl-16429157
ABSTRACT
We have discovered that beta-III spectrin (SPTBN2) mutations cause spinocerebellar ataxia type 5 (SCA5) in an 11-generation American kindred descended from President Lincoln's grandparents and two additional families. Two families have separate in-frame deletions of 39 and 15 bp, and a third family has a mutation in the actin/ARP1 binding region. Beta-III spectrin is highly expressed in Purkinje cells and has been shown to stabilize the glutamate transporter EAAT4 at the surface of the plasma membrane. We found marked differences in EAAT4 and GluRdelta2 by protein blot and cell fractionation in SCA5 autopsy tissue. Cell culture studies demonstrate that wild-type but not mutant beta-III spectrin stabilizes EAAT4 at the plasma membrane. Spectrin mutations are a previously unknown cause of ataxia and neurodegenerative disease that affect membrane proteins involved in glutamate signaling.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Ataxias Espinocerebelosas
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Proteínas del Citoesqueleto
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Proteínas del Tejido Nervioso
Tipo de estudio:
Observational_studies
Límite:
Adolescent
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Adult
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Aged
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Aged80
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Animals
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Child
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Nat Genet
Asunto de la revista:
GENETICA MEDICA
Año:
2006
Tipo del documento:
Article