2. Academic Validation
  3. Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling

Membrane trafficking. Nucleoside diphosphate kinases fuel dynamin superfamily proteins with GTP for membrane remodeling

  • Science. 2014 Jun 27;344(6191):1510-5. doi: 10.1126/science.1253768.
Mathieu Boissan 1,  Guillaume Montagnac 2,  Qinfang Shen 3,  Lorena Griparic 3,  Jérôme Guitton 4,  Maryse Romao 5,  Nathalie Sauvonnet 6,  Thibault Lagache 7,  Ioan Lascu 8,  Graça Raposo 5,  Céline Desbourdes 9,  Uwe Schlattner 9,  Marie-Lise Lacombe 10,  Simona Polo 11,  Alexander M van der Bliek 3,  Aurélien Roux 12,  Philippe Chavrier 13
Affiliations

Affiliations

  • 1 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. [email protected] [email protected].
  • 2 Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France.
  • 3 Department of Biological Chemistry, David Geffen School of Medicine at University of California, Los Angeles, Los Angeles, CA, USA.
  • 4 Hospices Civils de Lyon, Pierre Bénite, France. Université de Lyon, Lyon, France.
  • 5 Institut Curie, Research Center, Paris, France. Structure and Membrane Compartments, CNRS UMR 144, Paris, France.
  • 6 Institut Pasteur, Unité de Biologie des Interactions Cellulaires, Paris, France.
  • 7 Quantitative Image Analysis Unit, Institut Pasteur, Paris, France.
  • 8 Institut de Biochimie et Génétique Cellulaires-CNRS, Université Bordeaux 2, Bordeaux, France.
  • 9 Université Grenoble Alpes, Laboratory of Fundamental and Applied Bioenergetics, Grenoble, France. Inserm, U1055, Grenoble, France.
  • 10 Université Pierre et Marie Curie, University Paris 06, Paris, France. Saint-Antoine Research Center, INSERM UMR-S 938, Paris, France.
  • 11 IFOM, Fondazione Istituto FIRC di Oncologia Molecolare, Milan, Italy. Dipartimento di Scienze della Salute, Universita' degli Studi di Milano, Milan, Italy.
  • 12 Biochemistry Department, University of Geneva, & Swiss National Center for Competence in Research Program Chemical Biology, Geneva, Switzerland.
  • 13 Institut Curie, Research Center, Paris, France. Membrane and Cytoskeleton Dynamics, CNRS UMR 144, Paris, France. [email protected] [email protected].
PMID: 24970086 DOI: 10.1126/science.1253768
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.

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