Biology Reference
In-Depth Information
RGS2/RGS4 that are recruited to the seven-transmembrane domain receptor complex by
spinophilin [Liu et al., 2006].
Plasticity in dendritic spines may underlie learning and memory. Conditioned taste
aversion learning (CTA) is a form of associative learning. CTA acquisition and retention has
been previously associated to several regions of the central nervous system but not with
hippocampus.
Spinophilin KO mice had intact sensory processing whereas CTA is
significantly impaired compared to wild-type littermates. These observations have shown that
spinophilin plays a role in associative learning ability in vivo [Stafstrom-Davis et al., 2001].
Among the members of the spinophilin interactome two others proteins were suggested to
be involved in synaptic plasticity. TRPC5 and TRPC6 Ca
2+
/cation selective channels may
play a critical role in sculpting the electrical response to neurotransmitter in dendritic spines
[Goel et al., 2005]. TGN38 is a putative cargo receptor that may transport proteins between
dendritic spine compartments and post-synaptic membrane. Direct interaction of spinophilin
with TGN38 may be essential for the trafficking of spine's proteins and so for plasticity of
glutamatergic synaptic transmission [Stephens and Banting, 1999; McNamara et al., 2004].
C
ONCLUSION
Spinophilin is a multifunctional protein that regulates excitatory synaptic transmission
and plasticity at PSD by targeting PP1c to AMPA and NMDA channels, promoting their
down regulation by dephosphorylation and also by modulating the structural organisation of
dendritic spines. In spinophilin, domains fulfill joint functions. PP1-binding and PDZ
domains target and anchor PP1c close to its synaptic substrates (AMPA and NMDA
receptors), the F-actin-binding domain concentrates spinophilin in PSD and coiled-coil
domain is involved in spinophilin multimerization.
Studies using KO mices provide evidence that spinophilin and neurabin 1 play different
roles in hippocampal synaptic plasticity. Spinophilin is involved in hippocampal LTD and not
in LTP whereas neurabin 1 contributes selectively to LTP but not LTD [Feng et al., 2000; Wu
et al., 2008]. Experiments made with KO mices established the same distinct roles for
spinophilin and neurabin 1 in dopamine-mediated plasticity in striatal neurons [Allen et al.,
2006].
One open question is what is the structural difference upon which the functional
difference observed in synaptic plasticity is based. An emerging notion is that spinophilin and
neurabin 1 may differentially affect their target proteins and perform quite distinctive function
in cell. For example, the two scaffolding proteins forms a functional pair of opposing
regulators that reciprocally regulate signalling intensity by seven-transmembrane domain
receptors [Wang et al., 2007].
Spinophilin has been implicated in the pathophysiology of several illness associated with
striatum or hippocampal formation. A number of illness are associated with abnormalities of
dopaminergic neurotransmission including Parkinson's disease. In a rat model, striatal
spinophilin levels decreased during normal ageing, phenomena that can contribute to
Parkinson's disease progression [Brown et al., 2005]. Spinophilin expression was
significantly altered in the hippocampal formation in patients with schizophrenia and mood
disorders [Law et al., 2004]. This result suggested the involvement of a postsynaptic
