Biology Reference
In-Depth Information
Chapter 11
R
EGULATION OF
S
YNAPTIC
P
LASTICITY BY THE
S
CAFFOLDING
P
ROTEIN
S
PINOPHILIN
D. Sarrouilhe
*
and T. Métayé
Institut de Physiologie et Biologie Cellulaires, Pôle Biologie Santé,
Université de Poitiers, France
A
BSTRACT
Spinophilin/neurabin 2 is a protein scaffold that targets protein phosphatase 1
catalytic subunit (PP1c) close to some of its substrates. Gene analysis and biochemical
approaches have contributed to define in spinophilin a number of distinct modular
domains, such as one F-actin-, a receptor- and a PP1c-binding domains, a
PSD95/DLG/zo-1 (PDZ) and three coiled-coil domains, that govern protein-protein
interactions. Spinophilin plays important functions in the nervous system where it is
implicated in spine morphology and density regulation, neuronal migration and synaptic
plasticity. Morphological studies and subcellular distribution analysis indicated that
spinophilin was enriched in dendritic spines in the postsynaptic density (PSD). The
spinophilin interactome includes the glutamatergic α-amino-3-hydroxy-5-
methylisoxazole-4-propionic acid (AMPA) and N-methyl-D-aspartic acid (NMDA)
receptors that interact with the PDZ domain of the scaffolding protein. Studies using
spinophilin Knockout (KO) mice suggested that spinophilin serves to regulate excitatory
synaptic transmission and plasticity by targeting PP1c in the proximity of AMPA and
NMDA receptors, promoting their down-regulation by dephosphorylation and thus
regulating the efficiency of post-synaptic glutamatergic neurotransmission. The use of
spinophilin KO mice also provides evidence that spinophilin is a good candidate to serve
as a link between excitatory synapse transmission and changes in spine morphology and
density. The molecular mechanism that controls spine morphology was in part recently
elucidated and involved another spinophilin partner protein, the Rho-guanine nucleotide
exchange factor Lfc. This review presents the available data that are contributing to the
* Tel: +33 5 49 45 43 58; Fax: +33 5 49 45 43 58. E-mail address: Denis.Sarrouilhe@univ-poitiers.fr
