TY  - JOUR
AU  - Chivukula, Aparna Sharma
AU  - Suslova, Mariia
AU  - Kortzak, Daniel
AU  - Kovermann, Peter
AU  - Fahlke, Christoph
TI  - Functional consequences of SLC1A3 mutations associated with episodic ataxia 6
JO  - Human mutation
VL  - 41
IS  - 11
SN  - 1098-1004
CY  - New York, NY [u.a.]
PB  - Wiley-Liss
M1  - FZJ-2020-02814
SP  - 1892-1905
PY  - 2020
AB  - The episodic ataxias (EA) are a group of inherited neurological diseases characterized by paroxysmal cerebellar incoordination. There exist nine forms of episodic ataxia with distinct neurological symptoms and genetic origins. Episodic ataxia type 6 (EA6) differs from other EA forms in long attack duration, epilepsy and absent myokymia, nystagmus, and tinnitus. It has been described in seven families, and mutations in SLC1A3 , the gene encoding the glial glutamate transporter EAAT1, were reported in each family. How these mutations affect EAAT1 expression, subcellular localization and function and how such alterations result in the complex neurological phenotype of EA6 is insufficiently understood. We here compare the functional consequences of all currently known mutations by heterologous expression in mammalian cells, biochemistry, confocal imaging and whole‐cell patch clamp recordings of EAAT1 transport and anion currents. We observed impairments of multiple EAAT1 properties ranging from changes in transport function, impaired trafficking to increased protein expression. Many mutations caused only slight changes illustrating how sensitively the cerebellum reacts on impaired EAAT1 functions.
LB  - PUB:(DE-HGF)16
C6  - pmid:32741053
UR  - <Go to ISI:>//WOS:000567441900001
DO  - DOI:10.1002/humu.24089
UR  - https://juser.fz-juelich.de/record/878374
ER  -