Dominant-negative effects of episodic ataxia type 2 mutations involve disruption of membrane trafficking of human P/Q-type Ca2+ channels

2007 ◽  
Vol 214 (2) ◽  
pp. 422-433 ◽  
Author(s):  
Chung-Jiuan Jeng ◽  
Min-Chen Sun ◽  
Yi-Wen Chen ◽  
Chih-Yung Tang
Keyword(s):  
Membrane Trafficking ◽  
Dominant Negative ◽  
Episodic Ataxia ◽  
Negative Effects ◽  
Episodic Ataxia Type 2 ◽  
Ca2 Channels ◽  
Episodic Ataxia Type

scholarly journals Dominant-negative effects of human P/Q-type Ca2+ channel mutations associated with episodic ataxia type 2

2006 ◽  
Vol 290 (4) ◽  
pp. C1209-C1220 ◽  
Author(s):  
Chung-Jiuan Jeng ◽  
Yu-Ting Chen ◽  
Yi-Wen Chen ◽  
Chih-Yung Tang
Keyword(s):  
Dominant Negative ◽  
Episodic Ataxia ◽  
Molar Ratio ◽  
Loss Of Function ◽  
Negative Effects ◽  
Autosomal Dominant Disorder ◽  
Episodic Ataxia Type 2 ◽  
Episodic Ataxia Type ◽  
Suppression Effects

Episodic ataxia type 2 (EA2) is an inherited autosomal dominant disorder related to cerebellar dysfunction and is associated with mutations in the pore-forming α1A-subunits of human P/Q-type Ca2+ channels (Cav2.1 channels). The majority of EA2 mutations result in significant loss-of-function phenotypes. Whether EA2 mutants may display dominant-negative effects in human, however, remains controversial. To address this issue, five EA2 mutants in the long isoform of human α1A-subunits were expressed in Xenopus oocytes to explore their potential dominant-negative effects. Upon coexpressing the cRNA of α1A-WT with each α1A-mutant in molar ratios ranging from 1:1 to 1:10, the amplitude of Ba2+ currents through wild-type (WT)-Cav2.1 channels decreased significantly as the relative molar ratio of α1A-mutants increased, suggesting the presence of an α1A-mutant-specific suppression effect. When we coexpressed α1A-WT with proteins not known to interact with Cav2.1 channels, we observed no significant suppression effects. Furthermore, increasing the amount of auxiliary subunits resulted in partial reversal of the suppression effects in nonsense but not missense EA2 mutants. On the other hand, when we repeated the same coinjection experiments of α1A-WT and mutant using a splice variant of α1A-subunit that contained a considerably shorter COOH terminus (i.e., the short isoform), no significant dominant-negative effects were noted until we enhanced the relative molar ratio to 1:10. Altogether, these results indicate that for human WT-Cav2.1 channels comprising the long-α1A-subunit isoform, both missense and nonsense EA2 mutants indeed display prominent dominant-negative effects.

scholarly journals Novel missense variant of CACNA1A gene in a Slovak family with episodic ataxia type 2

2017 ◽  
Vol 161 (1) ◽  
pp. 107-110 ◽  
Author(s):  
Andrea Petrovicova ◽  
Miroslav Brozman ◽  
Egon Kurca ◽  
Tibor Gobo ◽  
Jana Dluha ◽  
...  
Keyword(s):  
Missense Variant ◽  
Episodic Ataxia ◽  
Episodic Ataxia Type 2 ◽  
Cacna1a Gene ◽  
Episodic Ataxia Type

Phenotypic Variability of Episodic Ataxia Type 2 Mutations: A Family Study

2010 ◽  
Vol 64 (2) ◽  
pp. 114-116 ◽  
Author(s):  
Julien Jung ◽  
Hervé Testard ◽  
Elisabeth Tournier-Lasserve ◽  
Florence Riant ◽  
Anne-Evelyne Vallet ◽  
...  
Keyword(s):  
Family Study ◽  
Phenotypic Variability ◽  
Episodic Ataxia ◽  
Episodic Ataxia Type 2 ◽  
Episodic Ataxia Type

scholarly journals Two Novel CACNA1A Gene Mutations Associated With Episodic Ataxia Type 2 and Interictal Dystonia

2005 ◽  
Vol 62 (2) ◽  
pp. 314 ◽  
Author(s):  
Sian D. Spacey ◽  
Luke A. Materek ◽  
Blajez I. Szczygielski ◽  
Thomas D. Bird
Keyword(s):  
Gene Mutations ◽  
Episodic Ataxia ◽  
Episodic Ataxia Type 2 ◽  
Cacna1a Gene ◽  
Episodic Ataxia Type

Rebound Upbeat Nystagmus After Lateral Gaze in Episodic Ataxia Type 2

2014 ◽  
Vol 13 (3) ◽  
pp. 411-413 ◽  
Author(s):  
Hyo-Jung Kim ◽  
Ji-Soo Kim ◽  
Jae-Hwan Choi ◽  
Jin-Hong Shin ◽  
Kwang-Dong Choi ◽  
...  
Keyword(s):  
Episodic Ataxia ◽  
Episodic Ataxia Type 2 ◽  
Upbeat Nystagmus ◽  
Episodic Ataxia Type

Premature stop codons in a facilitating EF-hand splice variant of CaV2.1 cause episodic ataxia type 2

2008 ◽  
Vol 32 (1) ◽  
pp. 10-15 ◽  
Author(s):  
Tracey D. Graves ◽  
Paola Imbrici ◽  
Esther E. Kors ◽  
Gisela M. Terwindt ◽  
Louise H. Eunson ◽  
...  
Keyword(s):  
Splice Variant ◽  
Episodic Ataxia ◽  
Stop Codons ◽  
Episodic Ataxia Type 2 ◽  
Ef Hand ◽  
Episodic Ataxia Type

Novel missense variant of CACNA1A gene: A case report of a family with episodic ataxia type 2

2017 ◽  
Vol 376 ◽  
pp. 119-120 ◽  
Author(s):  
Štefan Sivák ◽  
Egon Kurča ◽  
Adriána Krajčiová ◽  
Martina Hikkelová ◽  
Juraj Šimko ◽  
...  
Keyword(s):  
Case Report ◽  
Missense Variant ◽  
Episodic Ataxia ◽  
Episodic Ataxia Type 2 ◽  
Cacna1a Gene ◽  
Episodic Ataxia Type
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