The Role of Arrestins in Visual and Disease Processes of the Eye - Progress in Molecular Biology and Translational Science - page 240

arrestin1 principally localizes to the inner segments and transducin to the
outer segments. In response to light adaptation, arrestin1 moves to the outer
segments while transducin moves to the inner segments. This translocation
has been documented in every vertebrate retina that has been examined to
date, including rodents, primates, amphibians, and fish. Although arrestin1
translocation is most dramatic in rods, where the movement involves more
than 90% of the protein, arrestin4 translocation has also been demonstrated
in cones under appropriately bright illumination conditions. 44-48
Although first documented nearly three decades ago, 49 the functional
consequences of arrestin1 translocation for photoreceptors remain unre-
solved. Over the years, several hypotheses have been proposed. One possi-
bility is that the translocation of visual arrestins provides a mechanism to
regulate the dynamic sensitivity of photoreceptors, allowing a maximal
quantum response in dark-adapted photoreceptors when arrestin1 concen-
tration is lower in the outer segments, and either reducing response ampli-
tude or accelerating response recovery in light-adapted photoreceptors
when arrestin1 concentration is higher in outer segments (see Ref. 50 for
a discussion of photoreceptor adaptation). In mouse rods, arrestin1 translo-
cation is initiated at light levels causing a 3% bleach of the visual pigment,
which is nearly at the end of the dynamic range for rods at which point vision
shifts to cones. 51 Thus, there is some small potential for adaptive extension of
the rod response, although the time scale of arrestin1 translocation is likely
too slow to have a significant impact on rod adaptation. 52,53
Another potential function of arrestin1 translocation is preservation of
the rod photoreceptors during lighting conditions that are beyond the
dynamic response range of rods. 53 According to this hypothesis, the
increased concentration of arrestin1 in the light-adapted rod outer segment
would prevent phototransduction signaling from activated rhodopsin or sig-
naling by excess all- trans retinal that can also complex to opsin and activate
transducin. 54 This hypothesis is supported by studies in humans showing that
there is very slow recovery of rod function after a bright stimulation
(reviewed in Ref. 55 ). Such signaling inactivation would prevent the
long-term depletion of calcium in photoreceptors from extended cyclic
nucleotide-gated (CNG) channel closure that is known to initiate apoptosis
in photoreceptors. 56 Although this hypothesis is logical for rod photorecep-
tors, it is unclear what advantage is conferred on cones, which do not sat-
urate their light response and also support arrestin4 translocation. Clearly,
much work yet remains to decipher the functional consequences of arrestin1
and arrestin4 translocation in rod and cone photoreceptors.