Biology Reference
In-Depth Information
11. FUTURE PERSPECTIVES
As the chapters in this volume attest, research on arrestins has been
remarkably robust and multidisciplinary over the past decade. And the hori-
zons continue to expand at an exponential rate. What might we anticipate in
the next decade or so?
1. Cellular and in vivo experiments will continue to expand our understand-
ing of new functions of arrestins in signaling and trafficking not only of
7TMRs but also of other types of receptors and other categories of
macromolecules.
2.
The molecular mechanisms of b -arrestin-mediated signaling, endocyto-
sis, and other functions will be elucidated by detailed biochemical and
biophysical studies. The key to much of this will be application of con-
tinuously improving structural biology approaches, such as X-ray crys-
tallography, NMR, EPR, HDX, and many others to the study of
arrestins and their cellular partners. Structures of arrestin complexes with
their binding partners, for example, clathrin or MAP kinase components,
or of receptors in complex with arrestins, should elucidate how arrestins
mediate their diverse activities with atomic level detail.
3.
The therapeutic potential of targeting the arrestins, either through the
receptors with biased ligands or directly with small molecules or other
approaches, will be explored in numerous systems. Recent studies indi-
cating roles for arrestins in diverse diseases, such as chronic myelogenous
leukemia, 88 idiopathic pulmonary fibrosis, 89 and various cancers 90 have
recently presented a rationale for this latter approach.
As exciting as the first 25 years of research on arrestins has been, the next 25
should be even more so and proceed at an ever-increasing rate.
REFERENCES
1. Wacker WB, Donoso LA, KalsowCM, Yankeelov Jr JA, Organisciak DT. Experimental
allergic uveitis. Isolation, characterization, and localization of a soluble uveopathogenic
antigen from bovine retina. J Immunol . 1977;119:1949 - 1958.
2. Kuhn H. Light-regulated binding of rhodopsin kinase and other proteins to cattle pho-
toreceptor membranes. Biochemistry . 1978;17:4389- 4395.
3. Wilden U, Wust E, Weyand I, Kuhn H. Rapid affinity purification of retinal arrestin
(48 kDa protein) via its light-dependent binding to phosphorylated rhodopsin. FEBS
Lett . 1986;207:292- 295.
4. Miller JL, Fox DA, Litman BJ. Amplification of phosphodiesterase activation is greatly
reduced by rhodopsin phosphorylation. Biochemistry . 1986;25:4983 - 4988.
5. Zuckerman R, Cheasty JE. A 48 kDa protein arrests cGMP phosphodiesterase activation
in retinal rod disk membranes. FEBS Lett . 1986;297:35 - 41.
Search WWH ::




Custom Search