6533b7d8fe1ef96bd126a546

RESEARCH PRODUCT

The closure of Pak1-dependent macropinosomes requires the phosphorylation of CtBP1/BARS

Alberto LuiniAlexander SpaarDaniela CordaCarmen ValenteVarpu MarjomäkiRainer A. BöckmannGiuseppe PerinettiGabriele TuracchioElina KakkonenAntonino ColanziPrisca Liberali

subject

genetic structuresEndocytic cycleGTPaseBiologyTRANSCRIPTIONAL COREPRESSOREPIDERMAL GROWTH-FACTORArticleGeneral Biochemistry Genetics and Molecular BiologySYNAPTIC VESICLE ENDOCYTOSISMembrane fissionCell Line TumorMacropinocytic cupHumansPhosphorylationMacropinosomeMolecular BiologyDynaminEpidermal Growth FactorGeneral Immunology and MicrobiologyMEMBRANE FISSIONGeneral NeuroscienceActinsEnterovirus B HumanProtein Structure TertiaryTransport proteinCell biologyDNA-Binding ProteinsAlcohol OxidoreductasesProtein Transportp21-Activated KinasesPLASMA-MEMBRANEPinocytosisPhosphorylationCell Surface ExtensionsIntegrin alpha2beta1

description

Membrane fission is an essential process in membrane trafficking and other cellular functions. While many fissioning and trafficking steps are mediated by the large GTPase dynamin, some fission events are dynamin independent and involve C-terminal-binding protein-1/brefeldinA-ADP ribosylated substrate (CtBP1/BARS). To gain an insight into the molecular mechanisms of CtBP1/BARS in fission, we have studied the role of this protein in macropinocytosis, a dynamin-independent endocytic pathway that can be synchronously activated by growth factors. Here, we show that upon activation of the epidermal growth factor receptor, CtBP1/BARS is (a) translocated to the macropinocytic cup and its surrounding membrane, (b) required for the fission of the macropinocytic cup and (c) phosphorylated on a specific serine that is a substrate for p21-activated kinase, with this phosphorylation being essential for the fission of the macropinocytic cup. Importantly, we also show that CtBP1/BARS is required for macropinocytic internalization and infection of echovirus 1. These results provide an insight into the molecular mechanisms of CtBP1/BARS activation in membrane fissioning, and extend the relevance of CtBP1/BARS-induced fission to human viral infection.

yearjournalcountryeditionlanguage
2007-09-07The EMBO Journal
https://doi.org/10.1038/emboj.2008.59