Targeting of beta-arrestin2 to the centrosome and primary cilium: role in cell proliferation control.
BACKGROUND
The primary cilium is a sensory organelle generated from the centrosome in quiescent cells and found at the surface of most cell types, from where it controls important physiological processes. Specific sets of membrane proteins involved in sensing the extracellular milieu are concentrated within cilia, including G protein coupled receptors (GPCRs). Most GPCRs are regulated by beta-arrestins, betaarr1 and betaarr2, which control both their signalling and endocytosis, suggesting that betaarrs may also function at primary cilium.


RESULTS
In cycling cells, betaarr2 was observed at the centrosome, at the proximal region of the centrioles, in a microtubule independent manner. However, betaarr2 did not appear to be involved in classical centrosome-associated functions. In quiescent cells, both in vitro and in vivo, betaarr2 was found at the basal body and axoneme of primary cilia. Interestingly, betaarr2 was found to interact and colocalize with 14-3-3 proteins and Kif3A, two proteins known to be involved in ciliogenesis and intraciliary transport. In addition, as suggested for other centrosome or cilia-associated proteins, betaarrs appear to control cell cycle progression. Indeed, cells lacking betaarr2 were unable to properly respond to serum starvation and formed less primary cilia in these conditions.


CONCLUSIONS
Our results show that betaarr2 is localized to the centrosome in cycling cells and to the primary cilium in quiescent cells, a feature shared with other proteins known to be involved in ciliogenesis or primary cilium function. Within cilia, betaarr2 may participate in the signaling of cilia-associated GPCRs and, therefore, in the sensory functions of this cell "antenna".
Molla-Herman
Anahi
A
Institut Cochin, CNRS UMR 8104, Université Paris Descartes, Paris, France.
Boularan
Cedric
C
Ghossoub
Rania
R
Scott
Mark G H
MG
Burtey
Anne
A
Zarka
Marion
M
Saunier
Sophie
S
Concordet
Jean-Paul
JP
Marullo
Stefano
S
Benmerah
Alexandre
A
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D019390:Arrestins / Q000172:deficiency / Q000378:metabolism*; D054468:Axoneme / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D002502:Centrioles / Q000378:metabolism; D018385:Centrosome / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D051381:Rats; D000071557:beta-Arrestins
D048948:14-3-3 Proteins; D019390:Arrestins; C087415:KIF3A protein, human; D000071557:beta-Arrestins; D016547:Kinesins