Biology Reference
In-Depth Information
appreciation of spinophilin functions in synaptic plasticity and compares these functions
to those of the related structural protein neurabin 1.
A
BBREVIATIONS
AMPA: α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid; AR: adrenergic
receptor; CaMKII: Ca
2+
/calmodulin-dependent PK II;
CCK: cholecystokinin;
CD:
circular
dichroism;
DARPP-32:
dopamine- and cyclic AMP-regulated phosphoprotein, MW 32 kDa;
DCX: doublecortin; ERK: extracellular-signal regulated protein kinase; GEF: guanine
nucleotide exchange factors; KO: knockout; Lfc :Lbc[lymphoid blast crisis]'s first cousin;
LTD: long-term depression; LTP: long-term potentiation; MAPK: mitogen-activated protein
kinase; NMDA: N-methyl-D-aspartic acid; NMR: nuclear magnetic resonance; PDZ:
PSD95/DLG/zo-1; PK: protein kinase; PP: protein phosphatase; PP1c: PP1 catalytic subunit;
PSD: postsynaptic density; RGS: regulator of G-protein signalling; TGN: trans-Golgi
network; TRP: the transient receptor potential.
1.
I
NTRODUCTION
PP1 is a widespread expressed phosphoSerine/phosphoThreonine PP involved in many
cellular processes [Ceulemans and Bollen, 2004]. There are four isoforms of PP1c: PP1α,
PP1β, PP1γ1 and PP1γ2, the latter two arising through alternative splicing [Sasaki et al.,
1990]. PP1c can form complexes with up to 50 regulatory subunits converting the enzyme
into many different forms, which have distinct substrates specificities, restricted subcellular
locations and diverse regulations [Cohen, 2002]. In the nervous system, PP1 regulates short
term events such as the phosphorylation status of receptors, ion channels, and signalling
proteins, as well as long term events requiring changes in protein synthesis, gene expression,
and neuronal morphology that together modify neuronal plasticity. A novel PP1c binding
protein that is a potent modulator of PP1 activity was characterized in rat brain ten years ago
and named spinophilin [Allen et al., 1997]. In the same time, two novel actin filament-binding
proteins were purified from rat brain and named neurabin 1 and neurabin 2. Neurabin 2 was
further identified as spinophilin [Nakanishi et al., 1997] and neurabin 1 was shown to also
bind PP1c and to inhibit PP1c activity [McAvoy et al., 1999]. Spinophilin exhibits the
characteristics of scaffolding proteins with multiple protein interaction domains [Allen et al.,
1997; Sarrouilhe et al., 2006]. Scaffolding proteins link signalling enzymes, substrates and
potential effectors (such as channels, receptors) into a multiprotein signalling complex that
may be anchored to the cytoskeleton. Spinophilin has emerged as important scaffold linking
PP1c to a rapidly growing list of cellular proteins [Sarrouilhe et al., 2006]. Spinophilin and
neurabin 1 are highly enriched at the synaptic membrane in dendritic spines, the site of
excitatory neurotransmission, and thus may control PP1 functions during synaptic plasticity.
Moreover, among the spinophilin interactome some partner proteins are involved in synaptic
plasticity.
This review aims to outline the state of knowledge regarding spinophilin function in
synaptic plasticity and compares these functions to those of neurabin 1.
