Cooperative regulation of extracellular signal-regulated kinase activation and cell shape change by filamin A and beta-arrestins.: FLNA AND ßarr COOPERATE TO REGULATE ERK AND CELL SHAPE

14 pagesbeta-Arrestins (betaarr) are multifunctional adaptor proteins that can act as scaffolds for G protein-coupled receptor activation of mitogen-activated protein kinases (MAPK). Here, we identify the actin-binding and scaffolding protein filamin A (FLNA) as a betaarr-binding partner using Son of sevenless recruitment system screening, a classical yeast two-hybrid system, coimmunoprecipitation analyses, and direct binding in vitro. In FLNA, the betaarr-binding site involves tandem repeat 22 in the carboxyl terminus. betaarr binds FLNA through both its N- and C-terminal domains, indicating the presence of multiple binding sites. We demonstrate that betaarr and FLNA act cooperatively to activate the MAPK extracellular signal-regulated kinase (ERK) downstream of activated muscarinic M1 (M1MR) and angiotensin II type 1a (AT1AR) receptors and provide experimental evidence indicating that this phenomenon is due to the facilitation of betaarr-ERK2 complex formation by FLNA. In Hep2 cells, stimulation of M1MR or AT1AR results in the colocalization of receptor, betaarr, FLNA, and active ERK in membrane ruffles. Reduction of endogenous levels of betaarr or FLNA and a catalytically inactive dominant negative MEK1, which prevents ERK activation, inhibit membrane ruffle formation, indicating the functional requirement for betaarr, FLNA, and active ERK in this process. Our results indicate that betaarr and FLNA cooperate to regulate ERK activation and actin cytoskeleton reorganization

Identification de nouveaux partenaires d'interaction des b-arrestines (1-oligomérisation des b-arrestines)

PARIS7-Bibliothèque centrale (751132105) / SudocSudocFranceF

Homo- and Hetero-oligomerization of β-Arrestins in Living Cells

International audienceArrestins are important proteins, which regulate the function of serpentine heptahelical receptors and contribute to multiple signaling pathways downstream of receptors. The ubiquitous β-arrestins are believed to function exclusively as monomers, although self-association is assumed to control the activity of visual arrestin in the retina, where this isoform is particularly abundant. Here the oligomerization status of β-arrestins was investigated using different approaches, including co-immunoprecipitation of epitope-tagged β-arrestins and resonance energy transfer (BRET and FRET) in living cells. At steady state and at physiological concentrations, β-arrestins constitutively form both homo- and hetero-oligomers. Co-expression of β-arrestin2 and β-arrestin1 prevented β-arrestin1 accumulation into the nucleus, suggesting that hetero-oligomerization may have functional consequences. Our data clearly indicate that β-arrestins can exist as homo- and hetero-oligomers in living cells and raise the hypothesis that the oligomeric state may regulate their subcellular distribution and functions

Une histoire de la mémoire judiciaire

Si dans la mythologie grecque Clio est bien fille de Mémoire, une histoire de la mémoire judiciaire procède, à l’inverse, de la mémoire à son histoire, de l’Antiquité à nos jours. Associant archivistes, historiens, historiens du droit et juristes, ce volume met l’accent sur les questions d’enregistrement et de mémoire directement induites par l’activité des juges et des tribunaux. De l’écriture aux hommes qui tiennent la plume, de la production des actes aux lieux et aux aléas de leur conservation, de la mémoire judiciaire à ses usages ou à son utilité, trois points de vue convergents sont ainsi privilégiés pour explorer une question aux fortes implications contemporaines : la mise par écrit des actes de la vie judiciaire, la conservation pour « mémoire » des actes, enfin l’exploitation de cette mémoire institutionnelle pour l’écriture de l’histoire et l’apparition éventuelle d’autres formes, parallèles ou concurrentes, de mémoire de la vie judiciaire