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Merged (AMPAR + GFP)
1 m m
FIGURE 8.21 EphB signaling influences glutamate receptor aggregation in the central nervous system.
A. Cortical neurons were transfected with labeled EphB2 (green, left images) constructs, and exposed to
EphrinB1 or a control solution for one hour. The cultures were then fixed, and NMDA receptors (NMDAR)
were stained with antibody (red, center images). The merged images (right) show that EphrinB1 induced
NMDAR clusters on cortical neuron dendrites. B. Hippocampal neurons were cultured from wild-type or
triple EphB-deficient mice (EphB1-/-,EphB2-/-, EphB3-/-). The cells were transfected with green fluores-
cent protein (GFP) so that the dendrite could be observed, and AMPA receptors (AMPAR) were stained with
antibody (red, left images) after 21 days in vitro. Wild-type neurons exhibited punctate labeling of AMPAR
clusters all along the dendrites (merged images, right). In contrast, AMPAR clustering was not observed in
EphB-deficient neurons. (Adapted from Dalva et al., 2000; Henkemeyer et al., 2003)
gate within the membrane in gephyrin-deficient mice
(Feng et al., 1998). Gephyrin is also required for the clus-
tering of some (Kneussel et al., 1999), but not all (Levi et
al., 2004), GABA receptors.
Afamily of molecules with similar functional prop-
erties, called membrane-associated guanylate kinases
(MAGUKs), have been implicated in synapse forma-
tion throughout the nervous system (Cho et al., 1992;
Kistner et al., 1993). Synaptic channels and receptors
bind to amino acid sequences called the PDZ domains,
which are found on the N-terminal side. Similar to the
NMJ, cluster formation is regulated by protein phos-
phorylation. There is a specific 4 amino acid sequence
on the C-terminal tail of receptors and channels, called
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