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

Archive ouverte

Boissan, Mathieu | Montagnac, Guillaume | Shen, Qinfang | Griparic, Lorena | Guitton, Jérome | Romao, Maryse | Sauvonnet, Nathalie | Lagache, Thibault | Lascu, Ioan | Raposo, Graça | Desbourdes, Céline | Schlattner, Uwe | Lacombe, Marie-Lise | Polo, Simona | van Der Bliek, Alexander | Roux, Aurélien | Chavrier, Philippe

Edité par CCSD ; American Association for the Advancement of Science (AAAS) -

International audience. 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.

• Description
• Sujet/Public
• Outil
• Outil d'anticipation
• Mémoire et thèse
• Gestion