The Role of Arrestins in Visual and Disease Processes of the Eye - Progress in Molecular Biology and Translational Science - page 239

some cone photoreceptors contain both arrestin1 and arrestin4. Evidence of
this coexpression was first published in immunohistochemical analyses of
primate retinas in which arrestin1 immunoreactivity was clearly detected
in S-cones, but not in LM-cones. 40 This finding was more systematically
examined and confirmed in a detailed study showing that arrestin1 is present
in S-cones, and, surprisingly, is about 50-fold more concentrated in these
cones than arrestin4. 41 The cellular distributions of arrestin1 and arrestin4
in these cones are relatively similar with the exception that arrestin4 is more
highly concentrated in the synaptic pedicle than arrestin1.
The functional differences between arrestin1 and arrestin4 in cones are
not completely deciphered, but several facts are clear. First, cones require at
least one arrestin for normal recovery from strong flashes of light as cones
without either arrestin1 or arrestin4 saturate at lower light levels and have
prolonged recovery phases consistent with extended phosphodiesterase
activity. 41 Further, it is clear that either arrestin1 or arrestin4 is sufficient
to provide relatively normal response recovery dynamics to cones. 41 This
observation actually provides the first definitive evidence that arrestin4 func-
tions in the inactivation of cone visual pigments. What is not clear is whether
the two arrestins are fully redundant or have complementary roles. Perhaps
the function of the two arrestins in cones is related to the relative stability
of the arrestins in complex with the cone opsins, as arrestin4 has a much
higher rate of dissociation from activated cone opsin compared with
arrestin1 that forms more stable complexes. 42,43 Although there is not yet
any definitive evidence to support this conjecture, perhaps these different
stabilities provide a portion of the biochemical mechanism underlying the
enormous range of light intensities to which cones can respond, with
arrestin1 removing available visual pigment from potential activation and
arrestin4 remaining available to quench newly activated cone opsins.
5. TRANSLOCATION OF VISUAL ARRESTINS
In both rods and cones, the outer segment is a highly elaborated sen-
sory cilium specialized for transducing a photon into a change in membrane
potential that can be propagated to the visual cortex. Considering this
adaptation, it is not surprising that the biochemical components of the pho-
totransduction cascade are abundant in the outer segment. What is surpris-
ing, however, is that several of these components, most notably the visual
arrestins and transducin, undergo massive redistributions between the inner
and outer segments in response to lighting conditions. In dark-adapted rods,