« Paris en résonance » – Seminar

27 September 2019

Our next « Paris en résonance » seminar will be given by:

Sophie Zinn-Justin (Institute for Integrative Biology of the Cell – CEA Saclay)

Time: Tuesday, October 1st, at 12:30

Location: ENS, salle L361, Département de Physique

Title: Following phosphorylation events at the interface between the nuclear envelope and chromatin

Abstract: The molecular mechanisms that regulate genome organization in the mammalian interphase nucleus are largely unclear. At the interface between the nuclear membrane and chromatin, the inner nuclear envelope contains both nucleoskeleton filaments (lamins) and transmembrane proteins (NETs). Lamins tether heterochromatin to the nuclear envelope and modulate chromosome territory positions. Tissue specific expression of NETs also influences genome organization. Phosphorylation regulates localization and interactions of the nuclear envelope proteins during cell cycle and after a mechanical stress. We focused on a complex formed by lamin A/C, emerin (one of the best characterized NETs) and the chromatin binding protein BAF. These proteins contain intrinsically disordered regions (IDRs) that are highly phosphorylated in cells. We showed that BAF dimer mediates the interaction between lamin A/C and emerin, we solved the 3D structure of the complex(1), and we analysed the impact of cell cycle-dependent BAF phosphorylation by the kinase VRK1 on BAF structure and complex assembly. Emerin exibits a large IDR that is responsible for self-assembly and binding to structural proteins (lamin, actin, tubulin) (2). We also described the impact of mechano-dependent emerin tyrosine phosphorylation by the Src kinase on emerin structure and binding properties. Finally, we identified defective phosphorylation and binding events associated to muscular dystrophy(3) and premature ageing syndromes1.

References: (1) Samson et al., Nucleic Acids Res. 46, 10460-10473 (2018). (2) Samson et al., FEBS J. 284, 338-352 (2017). (3) Herrada et al., ACS Chem Biol. 10, 2733-2742 (2015).