Non-Conventional Functions of Nuclear Pores

Group leader

Nuclear Pore Complexes (NPCs) are elaborate structures embedded in the nuclear envelope and composed of multiple copies of about 30 different proteins termed nucleoporins (Nups). Our team aims at characterizing, beyond their well-established function in transport between the cytoplasm and the nucleus, non-conventional functions of nucleoporins, notably in cell division and differentiation.

Our previous studies had led to the characterization of a major structural complex of the NPC, the vertebrate Nup107-160 complex (Y-complex). We notably revealed the key function of this complex in NPC assembly, its interaction with kinetochore constituents, underlying its implication in various aspects of cell cycle progression, its intranuclear dynamics, and the implication of one of its constituents, Nup133 in cell differentiation during early embryogenesis.

We now aim to further characterize the functions, regulations, and direct partners of Y-Nups during cell cycle progression and cell differentiation. For this purpose, we combine cell imaging, biochemistry and genetics (CRISPR/Cas9-mediated knock-out/know-in strategies) in mammalian cells in human cancer cell lines but also mouse embryonic stem cells (mESCs). Indeed, the ESC model system, which is now well established in our team, enables us to perform functional studies in both pluripotent stem cells and in their differentiated derivatives.

From this research we expect to increase the current knowledge on the cellular pathway(s) by which Y-Nups mutations/deregulation lead to pathologies (notably nephrotic syndrome, neuro-developmental disorders, and cancer).

Current research topics:
- Nucleoporins and cell cycle
- Nucleoporins and embryonic stem cell differentiation
- Nucleoporin homeostasis in cancer cell lines

The team  is currently supported by the "Fondation pour la recherche Médicale" (French Foundation for Cancer Research (Equipe FRM 2015), and is part of the Labex “Who am I?

 

Valérie Doye was awarded the CNRS Silver Medal in 2009.

Selection of Publications (see all publications)

Cianciolo Cosentino C.*, Berto A*, Hari M, Loffing J, Neuhauss SCF, Doye V
Nucleoporin 133 deficiency leads to glomerular damage in zebrafish
[bioRxiv preprint]: first posted online Jun. 21, 2018
Abstract

Souquet B, Freed E, Berto A, Andric V, Audugé N, Reina-San-Martin B, Lacy E, Doye V.
Nup133 Is Required for Proper Nuclear Pore Basket Assembly and Dynamics in Embryonic Stem Cells.
Cell Rep. 2018 May 22;23(8):2443-2454.
Abstract

Berto A, Yu J, Morchoisne-Bolhy S, Bertipaglia C, Vallee R, Dumont J, Ochsenbein F, Guerois R, Doye V.
Disentangling the molecular determinants for Cenp-F localization to nuclear pores and kinetochores.
EMBO Rep. 2018 May;19(5). pii: e44742.
Abstract

Romana S, Radford-Weiss I, Lapierre JM, Doye V , Geoffroy MC .
Formation of Nup98-containing nuclear bodies in HeLa sublines is linked to genomic rearrangements affecting chromosome 11.
Chromosoma. 2016 Sep;125(4):789-805.
Abstract

Morchoisne-Bolhy S, Geoffroy MC, Bouhlel IB, Alves A, Audugé N, Baudin X, Van Bortle K, Powers MA, Doye V. (2015)
Intranuclear dynamics of the Nup107-160 complex.
Mol Biol Cell. 26(12):2343-56
Abstract

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