Biology Reference
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polypeptides. In all cases, however, the splice variants are present in the ret-
ina at approximately 5-10% of the amount of the full-length arrestin1. Inter-
estingly, splice variations also occur in arrestin4,
32
and in the nonvisual
arrestin2 and arrestin3,
33,34
and are similarly confined to the C-terminal
100 amino acids.
In vitro
binding studies showed that like full-length arrestin1, this trun-
cated form was selective for activated rhodopsin. But unlike the full-length
version, the splice variant form also binds unphosphorylated, activated rho-
dopsin with relatively high affinity.
28,35
The p44 variant of arrestin1 has dif-
ferent binding affinities for various forms of differentially phosphorylated
rhodopsin.
36
A recent crystal structure of bovine p44 shows that p44 is very
similar to the structure of arrestin1, with some differences in the loop struc-
tures that likely influence the different selectivities of the truncated splice
variant for unphosphorylated, activated rhodopsin.
37
All these studies
suggested that the splice variants might serve an auxiliary role in regulating
rhodopsin activity. However, a study of transgenic mice engineered to selec-
tively express either the full-length version of arrestin1 or the mouse ana-
logue of the bovine p44 splice form showed that either variant of
arrestin1 could quench the photoresponse equally well.
38
Surprisingly, only
the full-length version of arrestin1 could quench unphosphorylated, photo-
activated rhodopsin in contrast to what was predicted from
in vitro
binding
assays. The only other difference observed between the arrestin1 variants
was under very bright flash conditions, at which point the flash response
in rods expressing the splice variant of arrestin1 returned to baseline much
more slowly than in those expressing the full-length arrestin1. Perhaps this
difference in quenching relates to the slower rate of translocation seen in the
splice variants of arrestin1 (
see section 5 on
Arrestin Translocation
below
) with
the amount of activated rhodopsin exceeding that of the available p44 and
exceeding the rate at which it can translocate into the outer segments to
quench rhodopsin.
4. ARRESTINS IN CONE PHOTORECEPTORS
Similar to rod photoreceptors, cone photoreceptors also have a pho-
totransduction cascade that is regulated by arrestin family members. The ini-
tial discovery of an arrestin family member, arrestin4, in pinealocytes that
was also highly expressed in cone photoreceptors led to the hypothesis that
rod phototransduction was regulated by arrestin1 and cone photo-
transduction by arrestin4.
6,7,39
Recent studies, however, have shown that
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