Trans-synaptic interaction of GluRdelta2 and Neurexin through Cbln1 mediates synapse formation in the cerebellum.
Cell
; 141(6): 1068-79, 2010 Jun 11.
Article
em En
| MEDLINE
| ID: mdl-20537373
ABSTRACT
Elucidation of molecular mechanisms that regulate synapse formation is required for the understanding of neural wiring, higher brain functions, and mental disorders. Despite the wealth of in vitro information, fundamental questions about how glutamatergic synapses are formed in the mammalian brain remain unanswered. Glutamate receptor (GluR) delta2 is essential for cerebellar synapse formation in vivo. Here, we show that the N-terminal domain (NTD) of GluRdelta2 interacts with presynaptic neurexins (NRXNs) through cerebellin 1 precursor protein (Cbln1). The synaptogenic activity of GluRdelta2 is abolished in cerebellar primary cultures from Cbln1 knockout mice and is restored by recombinant Cbln1. Knockdown of NRXNs in cerebellar granule cells also hinders the synaptogenic activity of GluRdelta2. Both the NTD of GluRdelta2 and the extracellular domain of NRXN1beta suppressed the synaptogenic activity of Cbln1 in cerebellar primary cultures and in vivo. These results suggest that GluRdelta2 mediates cerebellar synapse formation by interacting with presynaptic NRXNs through Cbln1.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Precursores de Proteínas
/
Sinapses
/
Cerebelo
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Receptores de Glutamato
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Moléculas de Adesão de Célula Nervosa
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Proteínas do Tecido Nervoso
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cell
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão