The Role of Arrestins in Visual and Disease Processes of the Eye - Progress in Molecular Biology and Translational Science - page 247

ubiquitinylated by parkin, 83,90 this has not yet been demonstrated for either
arrestin1 or arrestin4.
The visual arrestins have also been shown to bind to Mdm2, another
ubiquitin ligase classically involved in ubiquitination of the p53 tumor sup-
pressor. 83,88,89 Although both arrestin1 and arrestin4 associate with Mdm2
in tissue culture, 88,89 only arrestin1 appears to act as an adaptor molecule,
associating Mdm2 with microtubules. 67 Accordingly, only association of
Mdm2 with arrestin1, and not arrestin4, results in elevated ubiquitination
levels of proteins in the cytoskeletal fractions of transfected HEK-293 cells. 67
Although the interactions between visual arrestins and ubiquitin ligases are
clearly supported by strong empirical evidence, like the MAP kinases, there
has not yet been any clear indication if these interactions occur within pho-
toreceptors, and if so, what the functional consequences might be.

6.4. Calmodulin
Both arrestin1 and arrestin4 have been shown to bind calcium-occupied cal-
modulin. 91 Despite the relatively low affinity of visual arrestins for calmod-
ulin ( 7 m M), the high concentration of arrestin1 and arrestin4 in
photoreceptors (millimolar range) makes this association physiologically rel-
evant. Although calmodulin binds on the same surface of arrestin1 as does
activated rhodopsin, calmodulin does not appear to have any effect on
receptor binding. Consequently, the role of the arrestin-calmodulin inter-
action remains undefined, but perhaps it functions to either differentially
localize calmodulin in photoreceptors or perhaps regulate the availability
of calmodulin for other interactions, including regulating/modulating

CNG channels.

6.5. -ethylmaleimide-sensitive factor

Recently, the Craft laboratory identified a novel interaction for arrestin1
that likely explains the localization of arrestin1 in the synapses of photore-
ceptors. Using anti-arrestin1 antibodies to pull-down arrestin1-interacting
partners, Huang et al. identified an interaction between arrestin1 and
N -ethylmaleimide-sensitive factor (NSF). 92 The interaction with NSF
was validated by reversed immunoprecipitation assays as well as pull-down
assays with heterologously expressed and purified components. NSF is an
ATPase involved in membrane fusion and thus plays a critical role in the
transfer of membrane vesicles. 93 The interaction of arrestin1 with NSF
increases the ATPase activity of NSF, thus increasing the rate of disassembly

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