The Role of Arrestins in Visual and Disease Processes of the Eye - Progress in Molecular Biology and Translational Science - page 244

in the outer segments to drive diffusion to the outer segments, and thus
arrestin1 returns to the inner segments.
There remain two obvious unknowns associated with this signaling path-
way—how is PLC activated by light and how does PKC activation initiate
translocation? The most parsimonious explanation for PLC activation is by
rhodopsin signaling either through transducin or an alternative G-protein.
Evidence supporting this idea comes from animal models lacking R9AP, a
regulator of G-protein signaling, which have prolonged G-protein activa-
tion. 51 In these animals, the light threshold for arrestin1 translocation is sig-
nificantly reduced, implicating the involvement of a G-protein. The identity
of this G-protein, however, is not precisely known, although there are
suggestive data. For example, animals lacking transducin a subunits show
an absence of threshold signaling of arrestin1 translocation, implicating
transducin as the signaling protein. 51 Further, pharmacological studies
indicate that arrestin1 translocation is sensitive to cholera toxin, 72 as is
transducin. 73 Additional studies will help define if transducin activation or
activation of another G-protein triggers arrestin1 translocation.
With regard to how PKC activation regulates the mobility of arrestin1,
there is currently no indication as to how this might occur although presum-
ably it is through PKC-mediated phosphorylation of a substrate that likely
resides in the transition zone and along the axoneme of the ciliary structure.
Although an earlier report indicated that arrestin1 translocation did not
require ATP, 61 subsequent reinvestigation in which ATP was more
completely depleted determined that ATP is essential for arrestin1 translo-
cation, consistent with PKC signaling through phosphorylation of an uni-
dentified target substrate. 72
6. NEW ROLES FOR ARRESTIN1 IN THE RETINA
Although many researchers thought the function of arrestin1 and
arrestin4 were well described when their role in visual pigment quenching
was identified, some puzzling features about the cell biology of visual
arrestins suggested that their function might be more complex. For example,
as described earlier, the localization of arrestin1 and arrestin4 is not static in
photoreceptors but changes between inner and outer segments in response
to lighting conditions. Further, when arrestin1 translocates to the outer seg-
ments during light adaptation, a significant fraction of arrestin1 remains
localized to the synaptic region in the inner plexiform layer. 45,52,74-76