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Cell Rep. 2018 May 29;23(9):2705-2717. doi: 10.1016/j.celrep.2018.04.112.

Neurobeachin and the Kinesin KIF21B Are Critical for Endocytic Recycling of NMDA Receptors and Regulate Social Behavior.

Author information

1
Department of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
2
Department of Synaptic Physiology, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
3
Department of Molecular Neurobiology, Max-Planck Institute for Experimental Medicine, Göttingen, Germany.
4
Cellular Proteomics Research Group, Helmholtz Centre for Infection Research (HZI), Braunschweig, Germany; Leibniz Institute for Analytical Sciences, ISAS, Dortmund, Germany.
5
Department of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. Electronic address: matthias.kneussel@zmnh.uni-hamburg.de.

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.

KEYWORDS:

KIF21B; NMDA receptor; Rab GTPase; autism spectrum disorder; dynein; endosomal recycling; neurobeachin; retromer; social behavior; synapse

PMID:
29847800
DOI:
10.1016/j.celrep.2018.04.112
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