Many cellular disorders are accompanied by changes in the morphology and positioning of intracellular organelles. Yet, the functional consequences of organelle alterations are often not clear. Organelles are the key feature of eukaryotic cells that constitute to a complex endomembrane system regulating cell homeostasis and function. Systematic studies on the organization and relative positioning of organelles are difficult, because, on the one hand, in vivo approaches are limited by the access of the samples, and on the other hand, in vitro cultured cells display strong morphological cell-to-cell variations. We use a minimal cell culture system based on micropatterning that provides adhesive cues for defined cell spreading and reduced cell-to-cell variations. We combine this controlled cell culture condition with precise quantification of organelle positioning using a density-based imaging approach. We have previously shown that endomembranes reveal a characteristic, well-defined, stable and reproducible organization in micropatterned cells. In this lecture, I will outline the molecular mechanisms by which endomembranes are positioned within cells. I will present how we have recently used our density-based approach on micropatterns to systematically analyze motor proteins that regulate Golgi apparatus positioning. I will also describe emerging tools that allow to precisely and dynamically control positioning of organelles. Finally, I will close my lecture describing new insights about organelle alterations during cancer progression.
1. Capmany A, Yoshimura A, Kerdous R, Caorsi V, Lescure A, Del Nery E, Coudrier E, Goud B, Schauer K. MYO1C stabilizes actin and facilitates the arrival of transport carriers at the Golgi complex. J Cell Sci. 2019 Apr 26;132(8).
2. Grossier JP, Xouri G, Goud B, Schauer K. Cell adhesion defines the topology of endocytosis and signaling. The EMBO Journal, 2014 Jan 1;33(1):35-45.
3. Duong T, Goud B, Schauer K. Closed-form density-based framework for automatic detection of cellular morphology changes. Proceedings of the National Academy of Sciences USA. 2012 May 29;109(22):8382-7.
4. Schauer K, Duong T, Bleakley K, Bardin S, Bornens M, Goud B. Probabilistic density maps to study global endomembrane organization. Nature Methods 2010 Jul;7(7):560-6.