Neurofilament-light increases the cell surface expression of the N-methyl-D-aspartate receptor and prevents its ubiquitination.
NMDA (N-methyl-D-aspartate) subtype of glutamate receptors are core components of dendritic spine postsynaptic densities (PSDs), in which they are anchored via their carboxy-terminal tails to cytoskeletal proteins. In this study, we examined the role of the neuronal intermediate filament protein, neurofilament-light (NF-L), also a component of the PSD, in the regulation of NMDA receptor (NMDAR) expression and function in a heterologous system. Coexpression of NF-L with NR1 or NR2B subunits of the NMDAR in HEK293 (human embryonic kidney 293) cells did not result in surface expression as measured by surface biotinylation and cell ELISAs, whereas the combined expression of the three elements resulted in a 20% increase in the surface abundance of NR1, along with a concomitant increase in NMDAR-mediated cytotoxicity. Investigating the origin of this increase, we found that the NR1 subunits are ubiquitinated in HEK293 cells, and that the coexpression of NF-L antagonizes this process. These results suggest a possible means of stabilization of NR1 via its association with NF-L.
Ratnam
Joseline
J
Department of Neurobiology, Weizmann Institute of Science, Rehovot, Israel.
Teichberg
Vivian I
VI
D002460:Cell Line; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins / Q000096:biosynthesis / Q000235:genetics; D016900:Neurofilament Proteins / Q000235:genetics / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000096:biosynthesis* / Q000235:genetics; D025801:Ubiquitin / Q000378:metabolism*
D008565:Membrane Proteins; D016900:Neurofilament Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D025801:Ubiquitin; C044882:neurofilament protein L