LRRTM3 Regulates Excitatory Synapse Development through Alternative Splicing and Neurexin Binding.
Cell Rep
; 14(4): 808-822, 2016 Feb 02.
Article
en En
| MEDLINE
| ID: mdl-26776509
ABSTRACT
The four members of the LRRTM family (LRRTM1-4) are postsynaptic adhesion molecules essential for excitatory synapse development. They have also been implicated in neuropsychiatric diseases. Here, we focus on LRRTM3, showing that two distinct LRRTM3 variants generated by alternative splicing regulate LRRTM3 interaction with PSD-95, but not its excitatory synapse-promoting activity. Overexpression of either LRRTM3 variant increased excitatory synapse density in dentate gyrus (DG) granule neurons, whereas LRRTM3 knockdown decreased it. LRRTM3 also controlled activity-regulated AMPA receptor surface expression in an alternative splicing-dependent manner. Furthermore, Lrrtm3-knockout mice displayed specific alterations in excitatory synapse density, excitatory synaptic transmission and excitability in DG granule neurons but not in CA1 pyramidal neurons. Lastly, LRRTM3 required only specific splice variants of presynaptic neurexins for their synaptogenic activity. Collectively, our data highlight alternative splicing and differential presynaptic ligand utilization in the regulation of LRRTMs, revealing key regulatory mechanisms for excitatory synapse development.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Moléculas de Adhesión Celular Neuronal
/
Empalme Alternativo
/
Potenciales Postsinápticos Excitadores
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2016
Tipo del documento:
Article