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As Nature is parsimonious and typically does not put proteins in remote
locations or change a protein's location without a purpose, these types of
observations have led various laboratories to expand their search for poten-
tial interactions for arrestin1 beyond activated rhodopsin. The list of these
binding partners for arrestin1 is growing annually.
6.1. Microtubules
Visual arrestin binding to microtubules was first demonstrated for arrestin1
and its shorter splice variant. 77 Subsequently, binding to microtubules has
been demonstrated for all members of the arrestin family. 67 The association
of arrestin1 with microtubules occurs through the same surface of arrestin1
that interacts with activated rhodopsin, and is thus mutually exclusive. 66,77
The affinity of arrestin1 is comparatively lower for microtubules (40 m M 66 )
than for activated phosphorhodopsin (50 nM 78 ). The binding occurs nearly
as well for the unpolymerized ab dimers of tubulin as for the polymerized
microtubules. 66 Unlike the binding of arrestin1 to rhodopsin, which occurs
only through the monomeric form of arrestin1, the binding to microtubules
can occur through either the monomeric or the tetrameric forms of
arrestin1. 64
The functional consequences of arrestin's interaction with microtubules
is unclear, but several hypotheses have been proposed. First, as described ear-
lier, the binding of arrestin1 to microtubules has been proposed as a mech-
anism for contributing to the concentration of arrestin1 to the inner
segments during dark adaptation. 61 Perhaps this serves as a reservoir that
can meet the rod's quenching requirements during high levels of photon
flux to preserve the cell from metabolic rundown since the relatively low
affinity of arrestin1 for microtubules allows it to quickly diffuse and bind
activated rhodopsin in the outer segments. Alternatively, the association
of arrestin1 with microtubules in photoreceptors could also function as a
scaffolding agent, a well-known function for arrestin2 and arrestin3 (see
Ref. 79 , for a recent review). For example, as previously discussed, arrestin1
associates with enolase1, perhaps forming a scaffolding structure that helps
maintain the glycolytic complex and retain its demonstrated association with
microtubules. 80,81 In addition, other binding partners have been identified
for arrestin1, such as parkin and JNK3 (discussed below), which apparently
associate with microtubules via their interaction with arrestin1 without
modification of their catalytic activity 82,83 consistent with a scaffolding func-
tion. Experimental evidence supports both of these proposed functions, but
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