Publication: Meeting report -Building the Cell 2018

Présentation

Cell biologists from all around the world gathered in Paris on the 26 to 28 September 2018 to participate in the 3rd international meeting ‘Building the Cell’. It was organized by Heĺeǹe Barelli, Arnaud Echard, Thierry Galli, Florence Niedergang, Manuel Theŕy and Marie Heĺeǹe Verlhac on behalf of the French Society for Cell Biology (SBCF) at the Institut Pasteur. Around 230 participants joined the meeting for stimulating talks, discussions, poster sessions, and a gala dinner on the Seine that included a music performance by the rock group ‘Membrane Band’. The unifying theme of the meeting was the development of creative multidisciplinary approaches to understand cellular life at different scales in a dynamic and quantitative manner. Here, we summarize the results presented at the meeting and the emerging ideas from the different sessions. The 3rd international meeting ‘Building the Cell’ (Fig. 1; Fig. 2) was divided into ten different sessions that covered a variety of topics including intracellular trafficking, cell division, cytoskeletal dynamics and cell mechanics, cancer and stem cell biology, embryonic development and tissue morphogenesis, neurobiology, and aggregates and phase transitions. A broad spectrum of modern approaches and experimental systems ranging from synthetic biology and stem cell technologies to 3D organoids and animal models was presented. The meeting highlighted some of the latest and novel findings in cell biology, often coupled to major methodological developments in quantitative microscopy and computational modelling, as well as cell and tissue micro-engineering. Membrane, intracellular trafficking and mechanics Thanks to the synchronized secretory retention using selective hooks (RUSH) system they developed a few years ago (Boncompain et al., 2012), Franck Perez and his team (Institut Curie, Paris, France) were able to identify specific ‘hot spots’ of protein secretion at focal adhesions (FAs) (Fourriere et al., 2018 preprint). The combination of the RUSH system and multispectral fluorescence live-cell imaging revealed that these hot spots emerge owing to a spatial bias in the delivery of exocytotic membranous vesicles that contain secreted proteins. Perez discussed that this bias is introduced because of two distinct cellular activities. First, because of microtubules (MTs) that grow from the cell center to the cell periphery and stochastically ‘target’ FAs. There, MTs pause and serve as transport routes for the targeted delivery of secretory vesicles. Second, through the Rab6-ELKS pathway, with Rab6 being systematically loaded onto post-Golgi vesicles and the ELKS complex being enriched at FAs. Interestingly, among the proteins secreted in this fashion are collagens, which are fundamental to the formation of the extracellular matrix (ECM) and promote FA formation. This suggests the existence of a hitherto unappreciated positive-feedback loop between FA assembly and localized deposition of structural proteins of the ECM. Along these lines, Sandrine Etienne-Manneville (Institut Pasteur, Paris, France) showed some interesting results that suggest a crucial role of MTs in the mechanosensitivity of cell migration: integrin-mediated cell-substrate interactions lead to stabilization of a subset of MTs. Cytoplasmic MTs often terminate at FAs, where they accumulate post-translational marks in the form of tubulin acetylation. This process is executed by the enzyme tubulin acetyltransferase αTAT1, which resides in the vicinity of FAs (Bance et al., 2018 preprint). Acetylated stable MTs linked to FAs serve as transport routes for selective delivery of Rab6-dependent membrane vesicles to FAs, which promotes FA turnover. Experimentally interfering with the stabilizing acetylation of MTs in the vicinity of FAs leads to defects in FA growth and cell migration. Thomas Wollert (Institut Pasteur, Paris, France) showed how selectivity in autophagy is regulated in yeast at a molecular level. By reconstituting the initiation of autophagy from purified components, he showed that the initiation of selective autophagy is intimately linked to the availability of autophagic cargo. Thus, the decision to generate a selective or a non-selective autophagosome is already made by the time of the biogenesis initiation.