Proline-rich transmembrane protein 2 specifically binds to GluA1 but has no effect on AMPA receptor-mediated synaptic transmission.
J Clin Lab Anal
; 36(2): e24196, 2022 Feb.
Article
em En
| MEDLINE
| ID: mdl-34997978
ABSTRACT
BACKGROUND:
Proline-rich transmembrane protein 2 (PRRT2) is a neuron-specific protein associated with seizures, dyskinesia, and intelligence deficit. Previous studies indicate that PRRT2 regulates neurotransmitter release from presynaptic membranes. However, PRRT2 can also bind AMPA-type glutamate receptors (AMPARs), but its postsynaptic functions remain unclear. METHODS ANDRESULTS:
Whole-exome sequencing used to diagnose a patient with mental retardation identified a nonsense mutation in the PRRT2 gene (c.649C>T; p.R217X). To understand the pathology of the mutant, we cloned mouse Prrt2 cDNA and inserted a premature stop mutation at Arg223, the corresponding site of Arg217 in human PRRT2. In mouse hippocampal tissues, Prrt2 interacted with GluA1/A2 AMPAR heteromers but not GluA2/A3s, via binding to GluA1. Additionally, Prrt2 suppressed GluA1 expression and localization on cell membranes of HEK 293T cells. However, when Prrt2 was overexpressed in individual hippocampal neurons using in utero electroporation, AMPAR-mediated synaptic transmission was unaffected. Deletion of Prrt2 with the CRIPR/Cas9 technique did not affect AMPAR-mediated synaptic transmission. Furthermore, deletion or overexpression of Prrt2 did not affect GluA1 expression and distribution in primary neuronal culture.CONCLUSIONS:
The postsynaptic functions of Prrt2 demonstrate that Prrt2 specifically interacts with the AMPAR subunit GluA1 but does not regulate AMPAR-mediated synaptic transmission. Therefore, our study experimentally excluded a postsynaptic regulatory mechanism of Prrt2. The pathology of PRRT2 variants in humans likely originates from defects in neurotransmitter release from the presynaptic membrane as suggested by recent studies.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de AMPA
/
Transmissão Sináptica
/
Proteínas de Membrana
/
Deficiência Intelectual
/
Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Adolescent
/
Animals
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Female
/
Humans
/
Male
Idioma:
En
Revista:
J Clin Lab Anal
Assunto da revista:
TECNICAS E PROCEDIMENTOS DE LABORATORIO
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China