A hot spot for hotfoot mutations in the gene encoding the δ2 glutamate receptor

Ying Wang, Shinji Matsuda, Valerie Drews, Takashi Torashima, Miriam H. Meisler, Michisuke Yuzaki

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The orphan glutamate receptor δ2 is selectively expressed in Purkinje cells and plays a crucial role in cerebellar functions. Recently, ataxia in the hotfoot mouse ho4J was demonstrated to be caused by a deletion in the δ2 receptor gene (Grid2) removing the N-terminal 170 arnino acids of the δ2 receptor. To understand how δ2 receptors function, we characterized mutations in eight additional spontaneously occurring hotfoot alleles of Grid2. The mouse Grid2 gene consists of 16 exons, spanning approximately 1.4 Mb. Genomic DNA analysis showed that seven hotfoot mutants had a deletion of one or more exons encoding the N-terminal domain of δ2 receptors. The exception is ho5J, which has a point mutation in exon 12. Deletions in ho7J, ho9J, ho11J and ho12J mice result in the in-frame deletion of between 40 and 95 amino acids. Expression of constructs containing these deletions in HEK293 cells resulted in protein retention in the endoplasmic reticulum or cis-Golgi without transport to the cell surface. Coimmunoprecipitation assays indicated that these deletions also reduce the intermolecular interaction between individual δ2 receptors. These results indicate that the deleted N-terminal regions are crucial for oligomerization of δ2 receptors and their subsequent transport to the cell surface of Purkinje cells. The relatively large size of the Grid2 gene may be one of the reasons why many spontaneous mutations occur in this gene. In addition, the frequent occurrence of in-frame deletions within the N-terminal domain in hotfoot mutants suggests the importance of this domain in the function of δ2 receptors.

Original languageEnglish
Pages (from-to)1581-1590
Number of pages10
JournalEuropean Journal of Neuroscience
Volume17
Issue number8
DOIs
Publication statusPublished - 2003 Apr
Externally publishedYes

Fingerprint

Glutamate Receptors
Exons
Mutation
Purkinje Cells
Genes
HEK293 Cells
Ataxia
Point Mutation
Endoplasmic Reticulum
Alleles
Amino Acids
Acids
DNA
Proteins

Keywords

  • Assembly
  • Ataxia
  • Cerebellum
  • Mutant
  • Purkinje cells

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

A hot spot for hotfoot mutations in the gene encoding the δ2 glutamate receptor. / Wang, Ying; Matsuda, Shinji; Drews, Valerie; Torashima, Takashi; Meisler, Miriam H.; Yuzaki, Michisuke.

In: European Journal of Neuroscience, Vol. 17, No. 8, 04.2003, p. 1581-1590.

Research output: Contribution to journalArticle

Wang, Ying ; Matsuda, Shinji ; Drews, Valerie ; Torashima, Takashi ; Meisler, Miriam H. ; Yuzaki, Michisuke. / A hot spot for hotfoot mutations in the gene encoding the δ2 glutamate receptor. In: European Journal of Neuroscience. 2003 ; Vol. 17, No. 8. pp. 1581-1590.
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