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of the SNARE complexes involved in synaptic exocytosis. Because NSF and
arrestin1 interactions are at their peak in dark-adapted rods, the hypothe-
sized role of arrestin1 interaction with NSF is to sustain the release of syn-
aptic vesicles required by rod photoreceptors which are depolarized in the
dark and constantly releasing
L
-glutamate until a light response leads to a
graded diminution of transmitter release. Consistent with this hypothesis,
in mice deficient for arrestin1, there is no increase in photopic b-wave
amplitude of the electroretinogram in response to increasing light intensities,
indicating an absence of change in the synaptic transmission from rod and
cone cells to the bipolar cells.
92,94
Interestingly, NSF also localizes to the
photoreceptor ciliary transition zone, raising the potential that its multiple
interactions with proteins may have a role in protein trafficking through
the cilium.
95
Despite the overall structural homology between arrestin1 and arrestin4,
only arrestin1 interacts with NSF as demonstrated
in vitro
and
in vivo.
92
Inter-
estingly, an interaction with NSF has been previously noted in the arrestin
family for arrestin2 (
b
-arrestin1), although here the functional mechanism
seems different as arrestin2 appears to modulate clathrin-mediated receptor
endocytosis
96
and there is no evidence for interaction of arrestin1 with
clathrin.
6.6. Enolase1
Using an alternative approach to identifying potential interaction partners,
chemical cross-linking agents were utilized to tether arrestin1 to interacting
elements. Using dithiobis(succinimidylpropionate) as the cross-linker,
Smith
et al.
showed an association of arrestin1 with enolase1 in dark-adapted
rods.
68
This association was validated using a variety of techniques, including
coimmunoprecipitation and surface plasmon resonance. Importantly, the
surface plasmon resonance study used heterologously expressed and highly
purified arrestin1 and enolase1, demonstrating that the interaction between
these proteins is direct and does not require any additional scaffolding ele-
ments. An interaction between arrestin4 and enolase1 was also shown using
coimmunoprecipitation. There were two interesting observations made
about this interaction. First, arrestin1 modulates the glycolytic activity of
enolase1, decreasing its catalytic rate by as much as 25%; this is the first
known intersection of the phototransduction cascade and the glycolysis
pathway. The second observation is that while arrestin1 translocates in
response to light, enolase1 does not. Consequently, arrestin1 interacts with
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