title: Refilins are short-lived Actin-bundling proteins that regulate lamellipodium protrusion dynamics.
abstract: Refilins (RefilinA and RefilinB) are members of a novel family of Filamin binding proteins that function as molecular switches to conformationally alter the Actin filament network into bundles. We show here that Refilins are extremely labile proteins. An N-terminal PEST/DSG(X)2-4S motif mediates ubiquitin-independent rapid degradation. A second degradation signal is localized within the C-terminus. Only RefilinB is protected from rapid degradation by an auto-inhibitory domain that masks the PEST/DSG(X)2-4S motif. Dual regulation of RefilinA and RefilinB stability was confirmed in rat brain NG2 precursor cells (polydendrocyte). Using loss- and gain-of-function approaches we show that in these cells, and in U373MG cells, Refilins contribute to the dynamics of lamellipodium protrusion by catalysing Actin bundle formation within the lamella Actin network. These studies extend the Actin bundling function of the Refilin-Filamin complex to dynamic regulation of cell membrane remodelling.
authors.affiliation: INSERM U873 and INSERM Unité 1038, Grenoble F-38000, France CEA, BIG, BGE, Grenoble F-38000, France Université Grenoble Alpes, Grenoble F-38000, France.
authors.forename: Olivia
authors.initials: O
authors.lastname: Gay
authors.affiliation: INSERM U873 and INSERM Unité 1038, Grenoble F-38000, France CEA, BIG, BGE, Grenoble F-38000, France Université Grenoble Alpes, Grenoble F-38000, France.
authors.forename: Benoît
authors.initials: B
authors.lastname: Gilquin
authors.affiliation: INSERM U873 and INSERM Unité 1038, Grenoble F-38000, France CEA, BIG, BGE, Grenoble F-38000, France Université Grenoble Alpes, Grenoble F-38000, France.
authors.forename: Nicole
authors.initials: N
authors.lastname: Assard
authors.affiliation: INSERM U873 and INSERM Unité 1038, Grenoble F-38000, France Université Grenoble Alpes, Grenoble F-38000, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Stuelsatz
authors.affiliation: INSERM U873 and INSERM Unité 1038, Grenoble F-38000, France Université Grenoble Alpes, Grenoble F-38000, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Delphin
authors.affiliation: Genomic and Microgenomic Platform, ProfileXpert, Bron F-69676, France Lyon Neuroscience Research Center INSERM U1028/CNRS UMR 5292, Lyon F-69372, France.
authors.forename: Joël
authors.initials: J
authors.lastname: Lachuer
authors.affiliation: INSERM U873 and INSERM Unité 1038, Grenoble F-38000, France CEA, BIG, BGE, Grenoble F-38000, France Université Grenoble Alpes, Grenoble F-38000, France.
authors.forename: Xavier
authors.initials: X
authors.lastname: Gidrol
authors.affiliation: INSERM U873 and INSERM Unité 1038, Grenoble F-38000, France CEA, BIG, BGE, Grenoble F-38000, France Université Grenoble Alpes, Grenoble F-38000, France jacques.baudier@univ-amu.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Baudier
keywords: FAM101A; FAM101B; FilaminA; Polydendrocyte; RefilinA; RefilinB