Non-visual Arrestins Are Constitutively Associated with the Centrosome and Regulate Centrosome Function

In addition to regulating receptor activity, non-visual arrestins function as scaffolds for numerous intracellular signaling cascades and as regulators of gene transcription. Here we report that the two non-visual arrestins, arrestin2 and arrestin3, localize to the centrosome, a key organelle involv...

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Bibliographic Details
Published in:The Journal of biological chemistry 2010-03, Vol.285 (11), p.8316-8329
Main Authors: Shankar, Haripriya, Michal, Allison, Kern, Ronald C., Kang, Dong Soo, Gurevich, Vsevolod V., Benovic, Jeffrey L.
Format: Article
Language:English
Subjects:
Animals
Arrestin
Arrestins - genetics
Arrestins - metabolism
beta-Arrestins
Breast Neoplasms
Cattle
Cell Biology
Cell/Centrosome
Cell/Mitosis
Centrosome - metabolism
Fluorescent Antibody Technique
G Proteins/Coupled Receptors (GPCR)
Gene Knockdown Techniques
HeLa Cells
Humans
Interphase - physiology
Kidney - cytology
Methods/Confocal Microscopy
Microscopy, Confocal
Mitosis - physiology
Phosphatidylethanolamines
Receptors, G-Protein-Coupled - metabolism
RNA, Small Interfering
RNA/Interference/RNAi
Signal Transduction
Signal Transduction - physiology
Signal Transduction/Adapter Proteins
Transfection
Tubulin - metabolism
γ-Tubulin
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Summary:In addition to regulating receptor activity, non-visual arrestins function as scaffolds for numerous intracellular signaling cascades and as regulators of gene transcription. Here we report that the two non-visual arrestins, arrestin2 and arrestin3, localize to the centrosome, a key organelle involved in microtubule nucleation and bipolar mitotic spindle assembly. Both arrestins co-localized with the centrosomal marker γ-tubulin during interphase and mitosis and were found in purified centrosome preparations. In vitro binding assays demonstrated that both arrestins directly interact with γ-tubulin. Knockdown of either arrestin by RNA interference resulted in multinucleation, centrosome amplification, and mitotic defects, although only the loss of arrestin2 triggered aberrant microtubule nucleation. Importantly, overexpression of wild type arrestin rescued the multinucleation phenotype and restored normal centrosome number in arrestin siRNA-transfected cells. Moreover, overexpression of arrestin2 or -3 rescued the multinucleation defect observed in MDA-MB-231 breast cancer cells. Taken together, our data reveal that non-visual arrestins are novel centrosomal components and regulate normal centrosome function.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M109.062521