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Fig. 13.3
ORL1-N-type channel interaction at the plasma membrane. Prolonged receptor activa-
tion induces internalization of the ORL1 receptor and removal of the N-type channel/receptor
complex from the plasma membrane. As the ORL1 receptor undergoes internalization into lyso-
somes, N-type channels that are complexed with the receptor via their C-terminal tails, are likewise
internalized into lysosomal compartments for degradation
exogenous expression of D1R in HEK cells enhanced channel cell surface expres-
sion while dopamine treatment induced internalization of channel and receptor into
vesicles. In vitro binding assays detected a direct, biochemical interaction between
the intracellular loop-2, flanked by the third and fourth domain of the D1 receptor,
and the proximal portion of the Cav2.2 C terminus (Kisilevsky et al.
2008
) . This
work thus presented the novel concept that a GPCR was able to function as a chap-
erone protein for ion channels. The direct interaction not only optimized the recep-
tor-mediated regulation of the channel but also redirected the channel to a specific
subcellular compartment. A direct interaction with the N-type channels was also
observed for the D2R, but the physical link involved different regions as both the
II-III intracellular linker and C-terminal domain of the channel were shown to inter-
act with the third intracellular loop of D2R (Kisilevsky and Zamponi
2008
) . As
observed with ORL-1 receptor, D1 and D2 receptors functioned as chaperone pro-
teins of the channel to significantly improve its trafficking to the plasma membrane.
13.3
Other Examples of GPCR-Ion Channel Interactions
13.3.1
MaxiK Channels
Recent data has provided insights in the understanding of signaling complexes of
large-conductance calcium-activated potassium channels, MaxiK channels, in
vascular tone (Kume et al.
1992
; Scornik et al.
1993
). Despite the fact that these
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