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(i.e., in the dark). To this end, arrestin1 has been shown to interact directly
with microtubules 61,64,66,67 and with enolase1, 68 both of which are predom-
inantly inner segment proteins. Interestingly, the tetrameric form of
arrestin1 has been shown to bind microtubules without dissociation of
the tetramer. 64 The potential contribution of these binding partners to selec-
tive partitioning of arrestin1 to the inner segments during dark adaptation
has not yet been tested. In the end, the dark partitioning of arrestin1 to
the inner segments is likely complex, probably involving a combination
of both cytosolic exclusion and selective binding partners.
The structural elements of the arrestin1 protein that drive translocation
are primarily localized in the C-terminus of arrestin1. The first suggestion of
this structural feature was noted in the splice variants of arrestin1 which
showed a preferential localization to the outer segments in dark-adapted
bovine retinas compared to the full-length arrestin1. 29 Subsequent analysis
of the C-terminus showed that the C-terminal 30 amino acids of arrestin1
are essential for its proper localization, with the truncated version of arrestin1
preferentially partitioning to the outer segments of rod outer segments
regardless of lighting conditions. 69 Studies in transgenic mice expressing a
truncated form of arrestin1 missing the C-terminal 26 amino acids also dem-
onstrated that this truncated version of arrestin1 was significantly slower in
moving to the outer segments compared with the full-length arrestin1. 61 In
combination with the investigations of the diffusion-mediated movement of
arrestin1, these studies suggest that the C-terminus of arrestin1 is important
for interacting with whatever binding partner(s) is utilized for the par-
titioning of arrestin1 to the inner segments during dark adaptation.
Although diffusion is sufficient to explain much of the observed arrestin1
translocation, it appears that the complete process of arrestin1 translocation is
more complex and likely involves contributions from additional mecha-
nisms. Several studies have shown that disruption of cytoskeletal compo-
nents can affect certain aspects of arrestin1 translocation. In retinas treated
with microtubule depolymerizing agents, translocation of arrestin1 to the
outer segments during light adaptation is restricted to the proximal portion
of the outer segments in both mouse and frogs. 69,70 It is not clear if these
limits on translocation are a consequence of losing architectural elements
that maintain appropriate spacing of the distal discs for diffusional access or
are a result of disrupting a microtubule motor process that facilitates
arrestin1 translocation through the distal region of the outer segments.
It is intriguing that the distal outer segments use a different kinesin motor,
Kif17,
limited. 71
in the same region where arrestin1 translocation is
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