Membrane contact sites are cellular regions where two organelles come into proximity, facilitated by specific proteins that not only create a physical connection but also serve distinct functions like lipid transport, calcium signaling, or organelle inheritance. They exhibit diversity in their shapes, compositions, and dynamics, with intermembrane gaps spanning from 10 to 45 nm across distances up to several hundreds of nanometers. We are interested in the transport of cholesterol between ER and Golgi apparatus mediated by the tethering proteins, VAP-A and OSBP. We used cryo-electron tomography and advanced imaged analysis to get different 3D molecular architectures of in vitro reconstituted membrane contact sites. This also revealed the molecular requirement for the assembly-disassembly of protein complexes within a confined space between apposed organelles.
Beber A, Taveneau C, Nania M, et al. (2019) Membrane reshaping by micrometric curvature sensitive septin filaments. Nature communications 10(1): 420. de la Mora E, Dezi M, Di Cicco A, et al. (2021) Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites. Nature Communications 12(1): 3459. Subra M, Dezi M, Bigay J, et al. (2023) VAP-A intrinsically disordered regions enable versatile tethering at membrane contact sites. Developmental Cell 58(2): 121-138.e9.
Comprendre le fonctionnement des organismes vivants, telle est l’ambition du Centre de biologie intégrative (CBI), à Toulouse. Pour atteindre cet objectif, le CBI développe des approches multidisciplinaires, multi-échelles des molécules isolées aux organismes entiers et aux sociétés animales, et utilise de nombreux organismes modèles, des bactéries à l'homme.
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