title: ASB2α regulates migration of immature dendritic cells.
abstract: The actin-binding protein filamins (FLNs) are major organizers of the actin cytoskeleton. They control the elasticity and stiffness of the actin network and provide connections with the extracellular microenvironment by anchoring transmembrane receptors to the actin filaments. Although numerous studies have revealed the importance of FLN levels, relatively little is known about the regulation of its stability in physiological relevant settings. Here, we show that the ASB2α cullin 5-ring E3 ubiquitin ligase is highly expressed in immature dendritic cells (DCs) and is down-regulated after DC maturation. We further demonstrate that FLNs are substrates of ASB2α in immature DCs and therefore are not stably expressed in these cells, whereas they exhibit high levels of expression in mature DCs. Using ASB2 conditional knockout mice, we show that ASB2α is a critical regulator of cell spreading and podosome rosette formation in immature DCs. Furthermore, we show that ASB2(-/-) immature DCs exhibit reduced matrix-degrading function leading to defective migration. Altogether, our results point to ASB2α and FLNs as newcomers in DC biology.
authors: Centre National de la Recherche Scientifique, Université Paul Sabatier, Institut de Pharmacologie et de Biologie Structurale, Toulouse, France.
authors: Isabelle
authors: I
authors: Lamsoul
authors: Arnaud
authors: A
authors: Métais
authors: Emmanuelle
authors: E
authors: Gouot
authors: Mélina L
authors: ML
authors: Heuzé
authors: Ana-Maria
authors: AM
authors: Lennon-Duménil
authors: Christel
authors: C
authors: Moog-Lutz
authors: Pierre G
authors: PG
authors: Lutz
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D000818:Animals; D002465:Cell Movement / Q000235:genetics*; D003285:Contractile Proteins / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism / Q000502:physiology*; D064448:Filamins; D055785:Gene Knockdown Techniques; D055014:Granulocyte-Macrophage Progenitor Cells / Q000378:metabolism / Q000502:physiology; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D041681:NIH 3T3 Cells; D050826:Suppressor of Cytokine Signaling Proteins; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000235:genetics / Q000378:metabolism / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C542087:Asb2 protein, mouse; D003285:Contractile Proteins; D064448:Filamins; D007527:Isoenzymes; D008840:Microfilament Proteins; D050826:Suppressor of Cytokine Signaling Proteins; D044767:Ubiquitin-Protein Ligases