title: Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling.
abstract: Dynamin superfamily molecular motors use guanosine triphosphate (GTP) as a source of energy for membrane-remodeling events. We found that knockdown of nucleoside diphosphate kinases (NDPKs) NM23-H1/H2, which produce GTP through adenosine triphosphate (ATP)-driven conversion of guanosine diphosphate (GDP), inhibited dynamin-mediated endocytosis. NM23-H1/H2 localized at clathrin-coated pits and interacted with the proline-rich domain of dynamin. In vitro, NM23-H1/H2 were recruited to dynamin-induced tubules, stimulated GTP-loading on dynamin, and triggered fission in the presence of ATP and GDP. NM23-H4, a mitochondria-specific NDPK, colocalized with mitochondrial dynamin-like OPA1 involved in mitochondria inner membrane fusion and increased GTP-loading on OPA1. Like OPA1 loss of function, silencing of NM23-H4 but not NM23-H1/H2 resulted in mitochondrial fragmentation, reflecting fusion defects. Thus, NDPKs interact with and provide GTP to dynamins, allowing these motor proteins to work with high thermodynamic efficiency.
authors: Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France. Université Pierre et Marie Curie, University Paris 06, Paris, France. Saint-Antoine Research Center, INSERM UMR-S 938, Paris, France. mathieu.boissan@inserm.fr philippe.chavrier@curie.fr.
authors: Mathieu
authors: M
authors: Boissan
authors: Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France.
authors: Guillaume
authors: G
authors: Montagnac
authors: Department of Biological Chemistry, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
authors: Qinfang
authors: Q
authors: Shen
authors: Department of Biological Chemistry, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
authors: Lorena
authors: L
authors: Griparic
authors: Hospices Civils de Lyon, Pierre Bénite, France. Université de Lyon, Lyon, France.
authors: Jérôme
authors: J
authors: Guitton
authors: Institut Curie, Research Center, Paris, France. Structure and Membrane Compartments, CNRS UMR 144, Paris, France.
authors: Maryse
authors: M
authors: Romao
authors: Institut Pasteur, Unité de Biologie des Interactions Cellulaires, Paris, France.
authors: Nathalie
authors: N
authors: Sauvonnet
authors: Quantitative Image Analysis Unit, Institut Pasteur, Paris, France.
authors: Thibault
authors: T
authors: Lagache
authors: Institut de Biochimie et Génétique Cellulaires-CNRS, Université Bordeaux 2, Bordeaux, France.
authors: Ioan
authors: I
authors: Lascu
authors: Institut Curie, Research Center, Paris, France. Structure and Membrane Compartments, CNRS UMR 144, Paris, France.
authors: Graça
authors: G
authors: Raposo
authors: Université Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France. Inserm, U1055, Grenoble, France.
authors: Céline
authors: C
authors: Desbourdes
authors: Université Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France. Inserm, U1055, Grenoble, France.
authors: Uwe
authors: U
authors: Schlattner
authors: Université Pierre et Marie Curie, University Paris 06, Paris, France. Saint-Antoine Research Center, INSERM UMR-S 938, Paris, France.
authors: Marie-Lise
authors: ML
authors: Lacombe
authors: IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. Dipartimento di Scienze della Salute, Universita' degli Studi di Milano, Milan, Italy.
authors: Simona
authors: S
authors: Polo
authors: Department of Biological Chemistry, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
authors: Alexander M
authors: AM
authors: van der Bliek
authors: Biochemistry Department, University of Geneva, & Swiss National Center for Competence in Research Program Chemical Biology, Geneva, Switzerland.
authors: Aurélien
authors: A
authors: Roux
authors: Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France. mathieu.boissan@inserm.fr philippe.chavrier@curie.fr.
authors: Philippe
authors: P
authors: Chavrier
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D003034:Coated Pits, Cell-Membrane / Q000378:metabolism; D034281:Dynamins / Q000378:metabolism*; D004705:Endocytosis; D020558:GTP Phosphohydrolases / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008561:Membrane Fusion; D008928:Mitochondria / Q000378:metabolism; D054778:NM23 Nucleoside Diphosphate Kinases / Q000235:genetics / Q000378:metabolism*; D061107:Nucleoside Diphosphate Kinase D / Q000378:metabolism
chemical_list: D054778:NM23 Nucleoside Diphosphate Kinases; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; C517938:NME1 protein, human; C517940:NME2 protein, human; C517946:NME4 protein, human; D061107:Nucleoside Diphosphate Kinase D; D020558:GTP Phosphohydrolases; C415198:OPA1 protein, human; D034281:Dynamins