Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior.
Cell Rep
; 23(9): 2705-2717, 2018 05 29.
Article
en En
| MEDLINE
| ID: mdl-29847800
ABSTRACT
Autism spectrum disorders (ASDs) are associated with mutations affecting synaptic components, including GluN2B-NMDA receptors (NMDARs) and neurobeachin (NBEA). NBEA participates in biosynthetic pathways to regulate synapse receptor targeting, synaptic function, cognition, and social behavior. However, the role of NBEA-mediated transport in specific trafficking routes is unclear. Here, we highlight an additional function for NBEA in the local delivery and surface re-insertion of synaptic receptors in mouse neurons. NBEA dynamically interacts with Rab4-positive recycling endosomes, transiently enters spines in an activity-dependent manner, and regulates GluN2B-NMDAR recycling. Furthermore, we show that the microtubule growth inhibitor kinesin KIF21B constrains NBEA dynamics and is present in the NBEA-recycling endosome-NMDAR complex. Notably, Kif21b knockout decreases NMDAR surface expression and alters social behavior in mice, consistent with reported social deficits in Nbea mutants. The influence of NBEA-KIF21B interactions on GluN2B-NMDAR local recycling may be relevant to mechanisms underlying ASD etiology.
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Base de datos:
MEDLINE
Asunto principal:
Conducta Social
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Conducta Animal
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Proteínas Portadoras
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Cinesinas
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Receptores de N-Metil-D-Aspartato
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Endocitosis
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Proteínas del Tejido Nervioso
Idioma:
En
Revista:
Cell Rep
Año:
2018
Tipo del documento:
Article