Details

Autor(en) / Beteiligte

• López-Corcuera, Beatriz
• Arribas-González, Esther
• Aragón, Carmen

Titel

Hyperekplexia-associated mutations in the neuronal glycine transporter 2

Ist Teil von

• Neurochemistry international, 2019-02, Vol.123, p.95-100

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2019

Quelle

ScienceDirect

Beschreibungen/Notizen

• Hyperekplexia or startle disease is a dysfunction of inhibitory glycinergic neurotransmission characterized by an exaggerated startle in response to trivial tactile or acoustic stimuli. Although rare, this disorder can have serious consequences, including sudden infant death. One of the most frequent causes of hyperekplexia are mutations in the SLC6A5 gene, encoding the neuronal glycine transporter 2 (GlyT2), a key component of inhibitory glycinergic presynapses involved in synaptic glycine recycling though sodium and chloride-dependent co-transport. Most GlyT2 mutations detected so far are recessive, but two dominant missense mutations have been described. The detailed analysis of these mutations has revealed structural cues on the quaternary structure of GlyT2, and opens the possibility that novel selective pharmacochaperones have potential therapeutic effects in hyperekplexia. •Mutations in the neuronal glycine transporter 2 (GlyT2) gene SLC6A5 are cause of hyperekplexia.•Several aspects of GlyT2 function can be affected by mutations found in hyperekplexia patients.•Analysis of two dominant mutations unveils a role of the quaternary structure of GlyT2.