Biology Reference
In-Depth Information
fraction through their actin-binding domain. PP1γ1 and PP1α, but not PP1β, were enriched in
dendritic spines and the selectivity of spinophilin for these PP1c isoforms suggests that the
scaffold protein may contribute to the preferential targeting to PSD. Distinct populations of
dendritic spines can be observed in the primate cortex, containing either PP1α alone or both
PP1γ1 and PP1α suggesting different signalling properties. AMPA and NMDA glutamatergic
receptors are also highly enriched in dendritic spines.
Table 1. The main partner proteins of spinophilin involved in synaptic plasticity
Partner protein
Spinophilin motif
Functional consequence of the interaction
Actin polymer binding, cross-linking,
capping
F-actin
F-actin-binding domain
Spinophilin
coiled-coil domain
Actin cross-linking
Neurabin 1
coiled-coil domain
PP1α, PP1γ1
R-K-I-H-F motif
Targetting, activity regulation
Lfc
coiled-coil domain
Control of spine morphology
AMPA- and
NMDA-type
PDZ domain
Regulation of receptor phosphorylation
glutamate
receptor
TRPC5 and 6
Sculting electrical response to glutamate ?
TGN 38
coiled-coil domain
Post-synaptic membrane proteins trafficking
Glutamate receptor ion channels are abundantly expressed in the central nervous system
and mediate the majority of excitatory responses. There are 3 majors types of ionotropic
glutamate receptors called AMPA, NMDA and kainate. Four genes code for the AMPA
receptors (GluR1-4) and 7 genes code for the NMDA receptors (NR1, NR2A-D, NR3A and
NR3B). Alternative splicing from NR1 gene generates 8 different NR1 subunits. The gene
products can coassemble within families to generate a large number of heteromeric receptor
subtypes in vivo. Functional NMDA receptor is likely to be a tetramer composed most often
of two NR1 and two NR2 subunits of the same or different subtypes. In receptors containing
NR3 subunit, NR3 forms heterotetrameric complexes with NR1 and NR2 subunits [Mayer,
2005; Paoletti and Neyton, 2007]. AMPA receptor is a tetrameric assembly of dimers of the
GluR1-4 subunits. The composition of the receptor is not static and could be altered during
synaptic plasticity [Greger et al., 2007].
Long-lasting synaptic plasticity has been associated with brain development, learning and
memory. NMDA receptor-dependent long-term potentiation (LTP) and long-term depression
(LTD) in the CA1 region of the hippocampus have been the most extensively studied forms
of synaptic plasticity [Malenka and Bear, 2004]. It is now well accepted that in hippocampus
the triggering of the NMDA receptor-dependent form of LTP requires activation of the
receptor, the influx of Ca
2+
through the channel, a rise in Ca
2+
within the spine and an
activation of the CaMKII. The major mechanism for the expression of LTP involves changes
in the AMPA receptor trafficking allowing an increase of the number of receptor at synaptic
