Spectrin mutations cause spinocerebellar ataxia type 5.
Nat Genet. 2006-01-22; 38(2): 184-190
DOI: 10.1038/ng1728
Lire sur PubMed
1. Nat Genet. 2006 Feb;38(2):184-90. Epub 2006 Jan 22.
Spectrin mutations cause spinocerebellar ataxia type 5.
Ikeda Y(1), Dick KA, Weatherspoon MR, Gincel D, Armbrust KR, Dalton JC, Stevanin
G, Dürr A, Zühlke C, Bürk K, Clark HB, Brice A, Rothstein JD, Schut LJ, Day JW,
Ranum LP.
Author information:
(1)Department of Genetics, Cell Biology, and Development, University of
Minnesota, 321 Church St. SE, Minneapolis, Minnesota 55455 USA.
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.
DOI: 10.1038/ng1728
PMID: 16429157 [Indexed for MEDLINE]