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

Cell Reports
Kira V GromovaMatthias Kneussel

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.

Citations

Jan 25, 2020·Journal of Neurochemistry·Marta VieiraVictor Anggono
Sep 3, 2019·Frontiers in Cellular Neuroscience·Mona Katrin RoeslerWolfgang Wagner
Aug 8, 2019·Nature Communications·Abigail U CarbonellBryen A Jordan
May 7, 2020·Frontiers in Neuroanatomy·E Anne MartinAdam C Miller
Nov 17, 2020·Frontiers in Cellular Neuroscience·Chang Geon ChungSung Bae Lee
Mar 12, 2021·Journal of Human Genetics·Shiroh MiuraHiroki Shibata
May 26, 2021·Current Biology : CB·Jayne Aiken, Erika L F Holzbaur
Jul 28, 2021·Nature Genetics·Amy B WilfertEvan E Eichler
Oct 27, 2021·Addiction Biology·Verginia C Cuzon CarlsonRita P Cervera-Juanes
Nov 20, 2021·The FEBS Journal·Ruolin Fan, Kwok-On Lai

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