Your browser doesn't support javascript.
loading
The ER Stress Sensor PERK Coordinates ER-Plasma Membrane Contact Site Formation through Interaction with Filamin-A and F-Actin Remodeling.
van Vliet, Alexander R; Giordano, Francesca; Gerlo, Sarah; Segura, Inmaculada; Van Eygen, Sofie; Molenberghs, Geert; Rocha, Susana; Houcine, Audrey; Derua, Rita; Verfaillie, Tom; Vangindertael, Jeroen; De Keersmaecker, Herlinde; Waelkens, Etienne; Tavernier, Jan; Hofkens, Johan; Annaert, Wim; Carmeliet, Peter; Samali, Afshin; Mizuno, Hideaki; Agostinis, Patrizia.
Affiliation
  • van Vliet AR; Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, B-3000, Belgium.
  • Giordano F; Institut Jacques Monod-UMR 7592 CNRS-Université Paris Diderot, Paris Cedex 7, France.
  • Gerlo S; VIB Medical Biotechnology Center, UGent Department of Biochemistry, UGent, Gent B-9000, Belgium.
  • Segura I; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven B-3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven B-3000, Belgium.
  • Van Eygen S; Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, B-3000, Belgium.
  • Molenberghs G; Leuven Biostatistics and Statistical Bioinformatics Centre (L-BioStat), KU Leuven, Leuven, B-3000 Belgium.
  • Rocha S; Laboratory for Photochemistry and Spectroscopy, Department of Chemistry, KU Leuven, Leuven, B-3000 Belgium.
  • Houcine A; Institut Jacques Monod-UMR 7592 CNRS-Université Paris Diderot, Paris Cedex 7, France.
  • Derua R; Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, B-3000 Belgium; SyBioMa, KU Leuven, Leuven, B-3000 Belgium.
  • Verfaillie T; Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, B-3000, Belgium.
  • Vangindertael J; Laboratory for Photochemistry and Spectroscopy, Department of Chemistry, KU Leuven, Leuven, B-3000 Belgium.
  • De Keersmaecker H; Laboratory for Biomolecular Network Dynamics, Biochemistry, Department of Chemistry, KU Leuven, Leuven, B-3000 Belgium.
  • Waelkens E; Laboratory of Protein Phosphorylation and Proteomics, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, B-3000 Belgium; SyBioMa, KU Leuven, Leuven, B-3000 Belgium.
  • Tavernier J; VIB Medical Biotechnology Center, UGent Department of Biochemistry, UGent, Gent B-9000, Belgium.
  • Hofkens J; Laboratory for Photochemistry and Spectroscopy, Department of Chemistry, KU Leuven, Leuven, B-3000 Belgium.
  • Annaert W; VIB Center for Brain & Disease Research, Department of Neurosciences & Leuven Institute for Neuroscience and Disease (LIND), KU Leuven, Leuven B-3000, Belgium.
  • Carmeliet P; Laboratory of Angiogenesis and Vascular Metabolism, Department of Oncology, KU Leuven, Leuven B-3000, Belgium; Laboratory of Angiogenesis and Vascular Metabolism, Vesalius Research Center, VIB, Leuven B-3000, Belgium.
  • Samali A; Apoptosis Research Centre, NUI, Galway, Ireland.
  • Mizuno H; Laboratory for Biomolecular Network Dynamics, Biochemistry, Department of Chemistry, KU Leuven, Leuven, B-3000 Belgium.
  • Agostinis P; Laboratory of Cell Death Research and Therapy, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, B-3000, Belgium. Electronic address: patrizia.agostinis@kuleuven.be.
Mol Cell ; 65(5): 885-899.e6, 2017 Mar 02.
Article in En | MEDLINE | ID: mdl-28238652
Loss of ER Ca2+ homeostasis triggers endoplasmic reticulum (ER) stress and drives ER-PM contact sites formation in order to refill ER-luminal Ca2+. Recent studies suggest that the ER stress sensor and mediator of the unfolded protein response (UPR) PERK regulates intracellular Ca2+ fluxes, but the mechanisms remain elusive. Here, using proximity-dependent biotin identification (BioID), we identified the actin-binding protein Filamin A (FLNA) as a key PERK interactor. Cells lacking PERK accumulate F-actin at the cell edges and display reduced ER-PM contacts. Following ER-Ca2+ store depletion, the PERK-FLNA interaction drives the expansion of ER-PM juxtapositions by regulating F-actin-assisted relocation of the ER-associated tethering proteins Stromal Interaction Molecule 1 (STIM1) and Extended Synaptotagmin-1 (E-Syt1) to the PM. Cytosolic Ca2+ elevation elicits rapid and UPR-independent PERK dimerization, which enforces PERK-FLNA-mediated ER-PM juxtapositions. Collectively, our data unravel an unprecedented role of PERK in the regulation of ER-PM appositions through the modulation of the actin cytoskeleton.
Subject(s)
Key words
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Actin Cytoskeleton / Cell Membrane / Actins / EIF-2 Kinase / Endoplasmic Reticulum / Endoplasmic Reticulum Stress / Filamins Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2017 Type: Article Affiliation country: Belgium
Fulltext
Print
XML
PubMed Links
Search on Google

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Actin Cytoskeleton / Cell Membrane / Actins / EIF-2 Kinase / Endoplasmic Reticulum / Endoplasmic Reticulum Stress / Filamins Type of study: Prognostic_studies Limits: Animals / Humans Language: En Journal: Mol Cell Journal subject: BIOLOGIA MOLECULAR Year: 2017 Type: Article Affiliation country: Belgium