Publications

2018

• Evolutionary insights into Trm112-methyltransferase holoenzymes involved in translation between archaea and eukaryotes
  
  • Van tran Nhan
  • Muller Leslie
  • Ross Robert L
  • Lestini Roxane
  • Létoquart Juliette
  • Ulryck Nathalie
  • Limbach Patrick A
  • De crécy-Lagard Valérie
  • Cianférani Sarah
  • Graille Marc
  Nucleic Acids Research, Oxford University Press, 2018, 46 (16), pp.8483 - 8499. Protein synthesis is a complex and highly coordinated process requiring many different protein factors as well as various types of nucleic acids. All translation machinery components require multiple maturation events to be functional. These include post-transcriptional and post-translational modification steps and methylations are the most frequent among these events. In eukaryotes, Trm112, a small protein (COG2835) conserved in all three domains of life, interacts and activates four methyltransferases (Bud23, Trm9, Trm11 and Mtq2) that target different components of the translation machinery (rRNA, tRNAs, release factors). To clarify the function of Trm112 in archaea, we have characterized functionally and structurally its interaction network using Haloferax volcanii as model system. This led us to unravel that methyltransferases are also privileged Trm112 partners in archaea and that this Trm112 network is much more complex than anticipated from eukaryotic studies. Interestingly, among the identified enzymes, some are functionally orthologous to eukaryotic Trm112 partners, emphasizing again the similarity between eukaryotic and archaeal translation machineries. Other partners display some similarities with bacterial methyltransferases, suggesting that Trm112 is a general partner for methyltransferases in all living organisms. (10.1093/nar/gky638)
  DOI : 10.1093/nar/gky638
• GBF1 and Arf1 interact with Miro and regulate mitochondrial positioning within cells
  
  • Walch Laurence
  • Pellier Emilie
  • Leng Weihua
  • Lakisic Goran
  • Gautreau Alexis
  • Contremoulins Vincent
  • Verbavatz Jean-Marc
  • Jackson Catherine
  Scientific Reports, Nature Publishing Group, 2018, 8, pp.17121. The spatial organization of cells depends on coordination between cytoskeletal systems and intracellular organelles. The Arf1 small G protein and its activator GBF1 are important regulators of Golgi organization, maintaining its morphology and function. Here we show that GBF1 and its substrate Arf1 regulate the spatial organization of mitochondria in a microtubule-dependent manner. Miro is a mitochondrial membrane protein that interacts through adaptors with microtubule motor proteins such as cytoplasmic dynein, the major microtubule minus end directed motor. We demonstrate a physical interaction between GBF1 and Miro, and also between the active GTP-bound form of Arf1 and Miro. Inhibition of GBF1, inhibition of Arf1 activation, or overexpression of Miro, caused a collapse of the mitochondrial network towards the centrosome. The change in mitochondrial morphology upon GBF1 inhibition was due to a twofold increase in the time engaged in retrograde movement compared to control conditions. Electron tomography revealed that GBF1 inhibition also resulted in larger mitochondria with more complex morphology. Miro silencing or drug inhibition of cytoplasmic dynein activity blocked the GBF1-dependent repositioning of mitochondria. Our results show that blocking GBF1 function promotes dynein-and Miro-dependent retrograde mitochondrial transport along microtubules towards the microtubule-organizing center, where they form an interconnected network. (10.1038/s41598-018-35190-0)
  DOI : 10.1038/s41598-018-35190-0
• The trimeric coiled‐coil HSBP 1 protein promotes WASH complex assembly at centrosomes
  
  • Visweshwaran Sai
  • Thomason Peter
  • Guérois Raphaël
  • Vacher Sophie
  • Denisov Evgeny V
  • Tashireva Lubov
  • Lomakina Maria
  • Lazennec‐schurdevin Christine
  • Lakisic Goran
  • Lilla Sergio
  • Molinie Nicolas
  • Henriot Veronique
  • Mechulam Yves
  • Alexandrova Antonina
  • Cherdyntseva Nadezhda
  • Bièche Ivan
  • Schmitt Emmanuelle
  • Insall Robert
  • Gautreau Alexis
  EMBO Journal, EMBO Press, 2018, 37 (13), pp.e97706. The Arp2/3 complex generates branched actin networks that exert pushing forces onto different cellular membranes. WASH complexes activate Arp2/3 complexes at the surface of endosomes and thereby fission transport intermediates containing endocy-tosed receptors, such as a5b1 integrins. How WASH complexes are assembled in the cell is unknown. Here, we identify the small coiled-coil protein HSBP1 as a factor that specifically promotes the assembly of a ternary complex composed of CCDC53, WASH, and FAM21 by dissociating the CCDC53 homotrimeric precursor. HSBP1 operates at the centrosome, which concentrates the building blocks. HSBP1 depletion in human cancer cell lines and in Dictyos-telium amoebae phenocopies WASH depletion, suggesting a critical role of the ternary WASH complex for WASH functions. HSBP1 is required for the development of focal adhesions and of cell polarity. These defects impair the migration and invasion of tumor cells. Overexpression of HSBP1 in breast tumors is associated with increased levels of WASH complexes and with poor prognosis for patients. (10.15252/embj.201797706)
  DOI : 10.15252/embj.201797706
• The Arp2/3 Regulatory System and Its Deregulation in Cancer
  
  • Molinie Nicolas
  • Gautreau Alexis
  Physiological Reviews, American Physiological Society, 2018, 98 (1), pp.215-238. (10.1152/physrev.00006.2017)
  DOI : 10.1152/physrev.00006.2017