Calsyntenin-1 Affects Trafficking of
NMDA Receptor Subunits
Jeanne Ster, Martin Steuble, Clara Orlando,
Tu-My Diep, Alexander Akhmedov, et al.
(see pages 8716–8727)
Membrane proteins are transported in vesicles
that are carried along microtubules by
motor proteins. Motors interact with vesicles
by binding to adaptor proteins such as
calsyntenin-1, which couples vesicles to
kinesin-1 and is associated with early and
recycling endosomes. Previous studies suggested
a role for calsyntenins in synaptic
plasticity, prompting Ster et al. to examine
the effects of truncating calsyntenin-1 in
mice to prevent its interaction with kinesin.
In the hippocampus of juvenile mutant
mice, the frequency and slope of spontaneous
EPSPs were reduced compared to those
in controls, while long-term potentiation
was enhanced. These effects were attributable
to an increase in the synaptic levels of
NMDA receptor GluN2B subunits at the
expense of GluN2A subunits. GluN2A,
GluN2B, and GluN1 subunits all colocalized
with calsyntenin-1 in endosomes, suggesting
the trafficking of all three subunits
involves calsyntenin-1. However, the timing
of calsyntenin-1 expression and the effects
of the mutation suggest that calsyntenin-1 is
especially important for the postnatal increase
in GluN2A expression.