Thumbnail Image
Publication

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

Gromova, Kira V
; 
Muhia, Mary
; 
Rothammer, Nicola
; 
Gee, Christine E
; 
Thies, Edda
; 
Schaefer, Irina
; 
Kress, Sabrina
; 
Kilimann, Manfred W
; 
Shevchuk, Olga
; 
Oertner, Thomas G
... show 1 more
Citations
Altmetric:
Advisors
Editors
Other Contributors
Issue Date
2018-05-29
Submitted date
Show all metadata
Files
Thumbnail Image
Open Access publication
Adobe PDF, 5.01 MB
Other Titles
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.
Citation
Cell Rep. 2018 May 29;23(9):2705-2717. doi: 10.1016/j.celrep.2018.04.112
Affiliation
HZI, Helmholtz Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7, 38124 Braunschweig Germany.
Publisher
Elsevier
Journal
Cell Reports
URI
http://hdl.handle.net/10033/621747
DOI
10.1016/j.celrep.2018.04.112
PubMed ID
29847800
PubMed Central ID
Additional Links
Embedded video
Type
Article
Language
en
Description
Series/Report no.
ISSN
2211-1247
EISSN
ISBN
ISMN
Gov't Doc #
Sponsors
License
Attribution-NonCommercial-ShareAlike 4.0 International
cbn
Collections
publications of the research group cellular proteom research (CPRO)